text:
Alice in Wonderland syndrome

Alice in Wonderland syndrome (AIWS), also known as Todd's syndrome or dysmetropsia, is a neurological disorder that distorts perception. People with this syndrome may experience distortions in their visual perception of objects, such as appearing smaller (micropsia) or larger (macropsia), or appearing to be closer (pelopsia) or farther (teleopsia) than they are. Distortion may also occur for senses other than vision.

The cause of Alice in Wonderland syndrome is currently not known, but it has often been associated with migraines, head trauma, or viral encephalitis caused by Epstein–Barr virus infection. It is also theorized that AIWS can be caused by abnormal amounts of electrical activity, resulting in abnormal blood flow in the parts of the brain that process visual perception and texture.

Although there are cases of Alice in Wonderland syndrome in both adolescents and adults, it is most commonly seen in children.

Classification
The classification is not universally agreed upon in literature, however, some authors distinguish true Alice in Wonderland syndrome based solely on symptoms related to alterations in a person's body image. In contrast, they utilize the term "Alice in Wonderland-like syndrome" to encompass symptoms associated with changes in perception of vision, time, hearing, touch, or other external perceptions.

Due to the classification of all the clinical features seen in Alice in Wonderland, the table below illustrates theses features and symptoms by type with Type C having a combination of Type A and Type B symptoms.

Signs and symptoms
With over 60 associated symptoms, AIWS affects the sense of vision, sensation, touch, and hearing, as well as the perception of one's body image. Migraines, nausea, dizziness, and agitation are also commonly associated symptoms with Alice in Wonderland syndrome. Less frequent symptoms also include: loss of limb control and coordination, memory loss, lingering touch and sound sensations, and emotional instability. Alice in Wonderland syndrome is often associated with distortion of sensory perception, which involves visual, somatosensory, and non-visual symptoms. AIWS is characterized by the individual being able to recognize the distortion in the perception of their own body and is episodic. AIWS episodes vary in length from person to person. Episodes typically last from a few minutes to an hour, and each episode may vary in experience.

Visual distortions
Individuals with AIWS can experience illusions of expansion, reduction, or distortion of their body image, such as microsomatognosia (feeling that their own body or body parts are shrinking), or macrosomatognosia (feeling that their body or body parts are growing taller or larger). These changes in perception are collectively known as metamorphopsias, or Lilliputian hallucinations, which refer to objects appearing either smaller or larger than reality. People with certain neurological diseases may also experience similar visual hallucinations.

Within the category of Lilliputian hallucinations, people may experience either micropsia or macropsia. Micropsia is an abnormal visual condition, usually occurring in the context of visual hallucination, in which the affected person sees objects as being smaller than they are in reality. Macropsia is a condition where the individual sees everything larger than it is. These visual distortions are sometimes classified as "Alice in Wonderland-like syndrome" instead of true Alice in Wonderland syndrome but are often still classified as Alice in Wonderland syndrome by health professionals and researchers since the distinction is not official. Other distortions include teleopsia (objects are perceived further than they actually are) and pelopsia (objects are perceived closer than they actually are).

Depersonalization/derealization
Along with size, mass, and shape distortions of the body, those with Alice in Wonderland syndrome often experience a feeling of disconnection from one's own body, feelings, thoughts, and environment known as depersonalization/derealization. Depersonalization is a term specifically used to express a true detachment from their personal self and identity. It is described as being an observer completely outside of their own actions and behaviors. Derealization is seen as "dreamlike, empty, lifeless, or visually distorted." Drug and alcohol use can exacerbate this symptom into psychosis.

Hearing and time distortions
Individuals experiencing Alice in Wonderland syndrome can also often experience paranoia as a result of disturbances in sound perception. These disturbances can include the amplification of soft sounds or the misinterpretation of common sounds. Other auditory changes include distortion in pitch and tone and hearing indistinguishable and strange voices, noises, or music.

A person affected by AIWS may also lose a sense of time, a problem similar to the lack of spatial perspective brought on by visual distortion. This condition is known as tachysensia. For those with tachysensia, time may seem to pass very slowly, similar to an LSD experience, and the lack of time and space perspective can also lead to a distorted sense of velocity. For example, an object could be moving extremely slowly in reality, but to a person experiencing time distortions, it could seem that the object was sprinting uncontrollably along a moving walkway, leading to severe, overwhelming disorientation. Having symptoms of tachysensia is correlated with various underlying conditions, including substance use, migraine, epilepsy, head trauma, and encephalitis. Regardless of an individual's disease diagnosis, tachysensia is often included as a symptom associated with Alice in Wonderland Syndrome since it is classified as a perceptual distortion. Therefore, a person can be described as having Alice in Wonderland syndrome even if that person is experiencing tachysensia due to an underlying condition.

Causes
Because AlWS is not commonly diagnosed and documented, it is difficult to estimate what the main causes are. The cause of over half of the documented cases of Alice in Wonderland syndrome is unknown. Complete and partial forms of the AIWS exist in a range of other disorders, including epilepsy, intoxicants, infectious states, fevers, and brain lesions. Furthermore, the syndrome is commonly associated with migraines, as well as excessive screen use in dark spaces and the use of psychoactive drugs. It can also be the initial symptom of the Epstein–Barr virus (see mononucleosis), and a relationship between the syndrome and mononucleosis has been suggested. Within this suggested relationship, Epstein–Barr virus appears to be the most common cause in children, while for adults it is more commonly associated with migraines.

Infectious diseases
A 2021 review found that infectious diseases are the most common cause of Alice in Wonderland syndrome, especially in pediatrics. Some of these infectious agents included Epstein–Barr virus, Varicella Zoster virus, Influenza, Zika, Coxsackievirus, Plasmodium falciparum protozoa, and Mycoplasma pneumonia/Streptococcus pyogenes bacteria. The Association of Alice in Wonderland syndrome is most commonly seen with the Epstein-Barr virus. However, pathogenesis is not well understood beyond these reviews. In some instances, Alice in Wonderland syndrome was reported to be associated with an Influenza A infection.

Cerebral hypotheses
Alice in Wonderland syndrome can be caused by abnormal amounts of electrical activity resulting in abnormal blood flow in the parts of the brain that process visual perception and texture. Nuclear medical techniques using technetium, performed on individuals during episodes of Alice in Wonderland syndrome, have demonstrated that Alice in Wonderland Syndrome is associated with reduced cerebral perfusion in various cortical regions (frontal, parietal, temporal and occipital), both in combination and in isolation. One hypothesis is that any condition resulting in a decrease in perfusion of the visual pathways or visual control centers of the brain may be responsible for the syndrome. For example, one study used single photon emission computed tomography to demonstrate reduced cerebral perfusion in the temporal lobe in people with Alice in Wonderland syndrome.

Other theories suggest the syndrome is a result of non-specific cortical dysfunction (e.g. from encephalitis, epilepsy, decreased cerebral blood flow), or reduced blood flow to other areas of the brain. Other theories suggest that distorted body image perceptions stem from within the parietal lobe. This has been demonstrated by the production of body image disturbances through electrical stimulation of the posterior parietal cortex. Other researchers suggest that metamorphopsias, or visual distortions, may be a result of reduced perfusion of the non-dominant posterior parietal lobe during migraine episodes.

Throughout all the neuroimaging studies, several cortical regions (including the temporoparietal junction within the parietal lobe, and the visual pathway, specifically the occipital lobe) are associated with the development of Alice in Wonderland syndrome symptoms.[1]

Migraines
1 in 10 people who experience migraines have symptoms of Alice in Wonderland syndrome. The role of migraines in Alice in Wonderland syndrome is still not understood, but both vascular and electrical theories have been suggested. For example, visual distortions may be a result of transient, localized ischemia in areas of the visual pathway during migraine attacks. In addition, a spreading wave of depolarization of cells (particularly glial cells) in the cerebral cortex during migraine attacks can eventually activate the trigeminal nerve's regulation of the vascular system. The intense cranial pain during migraines is due to the connection of the trigeminal nerve with the thalamus and thalamic projections onto the sensory cortex. Alice in Wonderland syndrome symptoms can precede, accompany, or replace the typical migraine symptoms. Typical migraines (aura, visual derangements, hemicrania headache, nausea, and vomiting) are both a cause and an associated symptom of Alice in Wonderland Syndrome. Alice in Wonderland Syndrome is associated with macrosomatognosia which can mostly be experienced during migraine auras.

Genetic and environmental influence
While there currently is no identified genetic locus/loci associated with Alice in Wonderland syndrome, observations suggest that a genetic component may exist but the evidence so far is inconclusive. There is also an established genetic component for migraines which may be considered to be a possible cause and influence for hereditary Alice in Wonderland syndrome. Though most frequently described in children and adolescents, observational studies have found that many parents of children experiencing Alice in Wonderland syndrome have also experienced similar symptoms themselves, though often unrecognized. Family history may then be a potential risk factor for Alice in Wonderland syndrome.

One example of environmental influences on the incidence of Alice in Wonderland syndrome includes the drug use and toxicity of topiramate. Other reports of tyramine usage and the association with Alice in Wonderland syndrome has been reported but current evidence is inconclusive. Further research is required to establish the genetic and environmental influences on Alice in Wonderland syndrome.

The neuronal effect of cortical spreading depression (CSD) on TPO-C may demonstrate the link between migraines and Alice in Wonderland Syndrome. As children experience Alice in Wonderland Syndrome more than adults, it is hypothesized that structural differences in the brain between children and adults may play a role in the development of this syndrome.

Diagnosis
Alice in Wonderland syndrome is not part of any major classifications like the ICD-10 and the DSM-5. Since there are no established diagnostic criteria for Alice in Wonderland syndrome, and because Alice in Wonderland syndrome is a disturbance of perception rather than a specific physiological condition, there is likely to be a large degree of variability in the diagnostic process and thus it can be poorly diagnosed. Often, the diagnosis can be presumed when other causes have been ruled out. Additionally, Alice in Wonderland syndrome can be presumed if the patient presents symptoms along with migraines and complains of onset during the day (although it can also occur at night). Ideally, a definite diagnosis requires a thorough physical examination, proper history taking from episodes and occurrences, and a concrete understanding of the signs and symptoms of Alice in Wonderland syndrome for differential diagnosis. A person experiencing Alice in Wonderland syndrome may be reluctant to describe their symptoms out of fear of being labeled with a psychiatric disorder, which can contribute to the difficulty in diagnosing Alice in Wonderland syndrome. In addition, younger individuals may struggle to describe their unusual symptoms, and thus, one recommended approach is to encourage children to draw their visual illusions during episodes. Cases that are suspected should warrant tests and exams such as blood tests, ECG, brain MRI, and other antibody tests for viral antibody detection. Differential diagnosis requires three levels of conceptualization. Symptoms need to be distinguished from other disorders that involve hallucinations and illusions. It is usually easy to rule out psychosis as those with Alice in Wonderland syndrome are typically aware that their hallucinations and distorted perceptions are not 'real'. Once these symptoms are distinguished and identified, the most likely cause needs to be established. Finally, the diagnosed condition needs to be evaluated to see if the condition is responsible for the symptoms that the individual is presenting. Given the wide variety of metamorphopsias and other distortions, it is not uncommon for Alice in Wonderland syndrome to be misdiagnosed or confused with other etiologies.

Anatomical relation
An area of the brain that is important to the development of Alice in Wonderland syndrome is the temporal-parietal-occipital carrefour (TPO-C), where TPO-C region is the meeting point of temporooccipital, parietooccipital, and temporoparietal junctions in the brain. The TPO-C region is also crucial as it is the location where somatosensory and visual information are interpreted by the brain to generate any internal or external manifestations. Thus, modifications to these regions of the brain may trigger the cause of Alice in Wonderland Syndrome and body schema disorders simultaneously.

Depending on which portion of the brain is damaged, the symptoms of Alice in Wonderland syndrome may differ. For example, it has been reported that injury to the anterior portion of the brain is more likely to be correlated to more complex and a wider range of symptoms, whereas damage to the occipital region has mainly been associated with only simple visual disturbances.

Prognosis
The symptoms of Alice in Wonderland syndrome themselves are not physically harmful for the experiencer. Since there is no established treatment for Alice in Wonderland syndrome, prognosis varies between patients and is based on whether an underlying cause has been identified. In many cases, the intensity of the episodes and symptoms decline. Since it is predominately a benign condition, treatment isn't always required. Limitations of the prognosis of Alice in Wonderland syndrome are due to the disorder's low prevalence. Because of this, symptoms require careful evaluation and observation by healthcare professionals.

Some cases include reoccurring symptoms in which other medical conditions have to be ruled out before diagnosing AIWS If Alice in Wonderland Syndrome is caused by underlying conditions, symptoms typically occur during the underlying disease and can last from few days to months. In most cases, symptoms may disappear either spontaneously, with the treatment of underlying causes, or after reassurances that symptoms are momentary and harmless. In some cases it is experienced no more than a few episodes of symptoms, in other cases, symptoms may repeat several episodes before resolve. In rare cases, symptoms continue to manifest years after the initial experience, sometimes with the development of new visual disorders or migraines. These manifestations and distortions is why medication is then introduced but have some inducing effects.

Treatment
At present (2024), Alice in Wonderland Syndrome has no standardized treatment plan. Tests including electroencephalogram (EEG) and magnetic resonance imaging (MRI) are used to view brain activity to examine possible brain injury or deficits. Since symptoms of Alice in Wonderland syndrome often disappear, either spontaneously on their own, or with the treatment of the underlying disease, most clinical and non-clinical Alice in Wonderland Syndrome cases are considered to be benign. In cases of Alice in Wonderland syndrome caused by underlying chronic disease, however, symptoms tend to reappear during the active phase of the underlying cause (e.g., migraine, epilepsy). If treatment of Alice in Wonderland Syndrome is determined necessary and useful, it should be focused on treating the suspected underlying disease. Treatment of these underlying conditions mostly involves prescription medications such as antiepileptics, migraine prophylaxis, antivirals, or antibiotics. Antipsychotics are rarely used in treating Alice in Wonderland Syndrome symptoms due to their minimal effectiveness. There are also rare cases in which these prescription medications ,specifically antipsychotics, may worsen psychosis and psychotic symptoms due to the severity of distortions.

In 2011, a patient was examined for having verbal auditory hallucinations (VAHs) and functional MRI (fMRI) was employed to localize cerebral activity during self-reported VAHs. Repetitive transcranial magnetic stimulation (rTSMS) was used on the patient's Brodmann's area 40, in charge of meaning and phonology, at a frequency of 1 Hz at T3P3. After the second week of treatment, all VAHs and sensory distortions have no effected on the patient and went through a full remission. Follow up appointments were conducted with no signs of any symptoms. By month 8, the symptoms returned. A second treatment was done with complete remission.

Migraine prophylaxis
Treatment methods revolving around migraine prophylaxis include medications and following a low-tyramine diet. Drugs that may be used to prevent migraines include anticonvulsants, antidepressants, calcium channel blockers, and beta blockers. Other treatments that have been explored for migraines include repetitive transcranial magnetic stimulation (rTMS). However, further research is needed to establish the effectiveness of this treatment regime.

Epidemiology
The lack of established diagnostic criteria or large-scale epidemiological studies, low awareness of the syndrome, and the unstandardized diagnosis criteria and definition for Alice in Wonderland syndrome mean that the exact prevalence of the syndrome is currently unknown. One study on 3,224 adolescents in Japan demonstrated the occurrence of macropsia and micropsia to be 6.5% in boys and 7.3% in girls, suggesting that the symptoms of Alice in Wonderland syndrome may not be particularly rare. This also seems to suggest a difference in the male-to-female ratio of people with Alice in Wonderland syndrome. However, according to other studies, it appears that the male/female ratio is dependent on the age range being observed. Studies showed that younger males (age range of 5 to 14 years) were 2.69 times more likely to experience Alice in Wonderland syndrome than girls of the same age, while there were no significant differences between students of 13 to 15 years of age. Conversely, female students (16- to 18-year-olds) showed a significantly greater prevalence.

Alice in Wonderland syndrome is more frequently seen in children and young adults. The average age of the start of Alice in Wonderland syndrome is six years old, but it is typical for some people to experience the syndrome from childhood up to their late twenties. Because many parents who have Alice in Wonderland syndrome report their children having it as well, the condition is thought possibly to be hereditary. Some parents report not realizing they have experienced Alice in Wonderland syndrome symptoms until after their children have been diagnosed, further indicating that many cases of Alice in Wonderland syndrome likely go unrecognized and under-reported.

Research is still being expanded upon and developed on this syndrome in a multitude of different regions and specialties. Future studies are encouraged to include global collaborative efforts that may help improve understanding of Alice in Wonderland syndrome and its epidemiology.

History
The syndrome is sometimes called Todd's syndrome, about a description of the condition in 1955 by Dr. John Todd (1914–1987), a British consultant psychiatrist at High Royds Hospital at Menston in West Yorkshire. Dr. Todd discovered that several of his patients experienced severe headaches causing them to see and perceive objects as greatly out of proportion. In addition, they had altered sense of time and touch, as well as distorted perceptions of their own body. Despite having migraine headaches, none of these patients had brain tumors, damaged eyesight, or mental illness that could have accounted for these and similar symptoms. They were all able to think lucidly and could distinguish hallucinations from reality, however, their perceptions were distorted.

Dr. Todd speculated that author Lewis Carroll had used his own migraine experiences as a source of inspiration for his famous 1865 novel Alice's Adventures in Wonderland. Carroll's diary reveals that, in 1856, he consulted William Bowman, an ophthalmologist, about the visual manifestations of the migraines he regularly experienced. In Carroll's diaries, he often wrote of a "bilious headache" that came coupled with severe nausea and vomiting. In 1885, he wrote that he had "experienced, for the second time, that odd optical affection of seeing moving fortifications, followed by a headache". Carroll wrote two books about Alice, the heroine after which the syndrome is named. In the story, Alice experiences several strange feelings that overlap with the characteristics of the syndrome, such as slowing time perception. In chapter two of Alice's Adventures in Wonderland (1865), Alice's body shrinks after drinking from a bottle labeled "DRINK ME", after which she consumed a cake that made her so large that she almost touched the ceiling. These features of the story describes the macropsia and micropsia that are so characteristic to this disease.

These symptoms have been reported before in scientific literature, including World War I and II soldiers with occipital lesions, so Todd understood that he was not the first person to discover this phenomenon. Additionally, as early as 1933, other researchers such as Coleman and Lippman had compared these symptoms to the story of Alice in Wonderland. Caro Lippman was the first to hypothesize that the bodily changes that Alice encounters mimicked those of Lewis Carroll's migraine symptoms. Others suggest that Carroll may have familiarized himself with these distorted perceptions through his knowledge of hallucinogenic mushrooms. It has been suggested that Carroll would have been aware of mycologist Mordecai Cubitt Cooke's description of the intoxicating effects of the fungus Amanita muscaria (commonly known as the fly agaric or fly amanita), in his books The Seven Sisters of Sleep and A Plain and Easy Account of British Fungi.

Notable cases

 * In 2018 it was suggested that the Italian artist and writer Giorgio de Chirico may have suffered from the syndrome.

Gulliver's Travels
Alice in Wonderland syndrome's symptom of micropsia has also been related to Jonathan Swift's novel Gulliver's Travels. It has been referred to as "Lilliput sight" and "Lilliputian hallucination", a term coined by British physician Raoul Leroy in 1909.

Alice in Wonderland
Alice in Wonderland syndrome was named after Lewis Carroll's 19th-century novel Alice's Adventures in Wonderland. In the story, Alice, the titular character, experiences numerous situations similar to those of micropsia and macropsia. The thorough descriptions of metamorphosis clearly described in the novel were the first of their kind to depict the bodily distortions associated with the condition. There is some speculation that Carroll may have written the story using his own direct experience with episodes of micropsia resulting from the numerous migraines he was known to experience. It has also been suggested that Carroll may have had temporal lobe epilepsy.

House
The condition is diagnosed in the season 8 episode "Risky Business".

Secret Garden
In episode ten of Secret Garden (2010, Korean drama), the leading man, Kim Joo Won, suspects that he is suffering from Alice in Wonderland syndrome.

Doctors
In April 2020, a case of Alice in Wonderland syndrome was covered in an episode of the BBC daytime soap opera Doctors, when patient Hazel Gilmore (Alex Jarrett) experienced it.

title: Alice in Wonderland syndrome


text:
Icaria

Icaria, also spelled Ikaria (Ικαρία), is a Greek island in the Aegean Sea, 10 nautical miles (19 km) southwest of Samos.

Administratively, Icaria forms a separate municipality within the Ikaria regional unit, which is part of the North Aegean region. The principal town of the island and seat of the municipality is Agios Kirykos. The historic capitals of the island include Oenoe and Evdilos.

According to tradition, it derives its name from Icarus, the son of Daedalus in Greek mythology, who was believed to have fallen into the sea nearby.

Geography and climate
Icaria is one of the middle islands of the northern Aegean, 255.303 km2 in area with 102 mi of coastline and a population of 8,312 inhabitants. The topography is a contrast between verdant slopes and barren steep rocks. The island is mountainous for the most part. It is traversed by the Aetheras range, whose highest summit is 1037 m. Most of its villages are nestled in the plains near the coast, with some in the mountains.

Icaria has a tradition of producing strong red wine. Many parts of the island, especially the ravines, are covered in shrubbery, making the landscape lush with green. Aside from domestic and domesticated species such as goats, there are a number of small wild animals to be found, such as martens, European otters, jumping spiders, and green toads. Icaria exhibits a typical Mediterranean climate (Köppen: Csa).

History
Icaria has been inhabited since at least 7000 BC, when it was populated by the Neolithic Pelasgians, a blanket term used by the ancient Greeks to refer to all pre-Hellenic peoples inhabiting the Greek region. Around 750 BC, Greeks from Miletus colonized Icaria, establishing a settlement in the area of present-day Campos, which later became the ancient capital city of Oenoe. In antiquity, the island was called Icaria or Ikaria (Ἰκαρία), as today; and also Icarus or Ikaros (Ἴκαρος).

Antiquity
Icaria became part of the sea empire of Polycrates during the 6th century BC, and during the 5th century BC, the Icarian cities of Oenoe and Thermae were members of the Athenian-dominated Delian League. During the 2nd century, the island was colonized by Samos. At this time, the Tauropolion, the temple of Artemis was built at Oenoe.

Coins of the city represented Artemis and a bull. There was another, smaller temenos that was sacred to Artemis Tauropolos, at Nas, on the northwest coast of the island.

The sea around Icaria had a fearsome reputation among the Ancients. Homer likened its changeability to a crowd stirred by demagogy: "the gathering was stirred like the long sea-waves of the Icarian main, which the East Wind or the South Wind has raised, rushing upon them from the clouds of father Zeus" (Iliad II, 145), and Horace, too, in the opening of his Odes associates "the African winds as they fight the Icarian waves" with shattered ships (Odes I.i.15–6). The island itself had two associative descriptive epithets: ‘Dolichi' (elongated) and ‘Ichtheoussa' (rich in fish). The name may originally have come from the Phoenician word for fish, ‘ikor', rather than from associations with the mythical Icarus, whose fall was likely associated with the ancient deme of Icaria or Icarion in Attica.

In the later Fabulae ("stories") of Hyginus the Greek versions of myth associated with Melanippe (otherwise Arne) and her sons Boeotus and Aeolus by Poseidon are amended to relate the story of Theano (otherwise Autolyte), wife of Metapontus, a king of Icaria. Metapontus demanded that she bear him children, or leave the kingdom. She presented the exposed twin sons of Melanippe by Neptune to her husband, as if they were her own. Later Theano bore him two sons of her own and, wishing to leave the kingdom to her own children, sent them to kill Melanippe's while out hunting. In the fight that ensued, her two sons were killed, and she committed suicide upon hearing the news. Metapontus later married Melanippe and her two sons founded towns in Propontis called by their names — Boeotia and Aeolia.

Temple of Artemis at Nas
Nas had been a sacred spot to the pre-Hellenic inhabitants of the Aegean, and Nas was an important island port in antiquity, the last stop before testing the dangerous seas around Icaria. It was an appropriate location for sailors to make sacrifices to Artemis Tauropolos, who was a patron of seafarers; here, the goddess was represented in an archaic wooden xoanon.

The temple stood in good repair until the middle of the 19th century when the marble was pillaged, for their local church, by the Kato Raches villagers. In 1939, this church was excavated by the Greek archeologist Leon Politis. During the Axis occupation of Greece during World War II, many of the artifacts that were unearthed by Politis disappeared. Local tales state that the Germans and Italians stole the artifacts. According to local legend, marble artefacts from the temple still lie under the sand of the Nas beach where the temple stood.

In The Anabasis of Alexander, the second-century Greek historian Arrian recorded Aristobulus as saying that Alexander the Great had ordered that Failaka Island in the Persian Gulf should be called Icarus, after Icaria in the Aegean Sea.

Medieval Era
In the 14th century CE, Icaria was part of the Republic of Genoa's possessions in the Aegean. At some point during this period the Icarians destroyed their own ports to prevent the landing of unwanted visitors. According to local historians, the Icarians, based on their own designs, built seven watchtowers along the coastlines. Once an unknown or enemy vessel appeared, the observers would at once light a fire at the top and run to a tank which was always filled with water. A wooden plug located at the base was pulled, and water would flow. The guards of the other watchtowers were alerted by the fire and repeated the process. In the inner side of each tower's tank are marks identical to the ones measuring volumes in flasks. Each one of these marks was labelled with a different message on it, such as "pirate attack" or "unknown ship approaching". Once the water level reached the mark signifying the appropriate message, the messengers would place the plug back on the tank and put out the fire, so that each of the other towers could decode the size and gravity of the incoming danger. The watchtowers on the island's heights, such as the one in Drakano, were part of the islands' communication network since the time of the Delian League.

At the same time the Icarians rarely built their houses in the form prevalent today. Each house was low, had a single room, a roof of stone slabs, and was distant from neighbouring ones. It had a single low door and the sea-facing side was protected with tall walls, while there was an opening on the roof (locally called the Anefantis). Because a chimney with smoke could betray the house's location, it was often sealed. Smoke was poured through the roof slabs without being visible, while simultaneously clearing the wooden roof supports of insects. Rooms featured the bare necessities, such as a grinding stone and a cauldron. Traditionally, people would sleep on the floor and hide their belongings in the walls. Men and women wore almost the same clothing: sewn woollen skirts for women, a type of fustanella for the men. Later on the vest came to be worn by men and women. This frugal way of living contributed to the famed Icarian longevity and the absence of distinct social classes. Each house was self-sufficient, using the living space around it for the cultivation of the necessary things, women contributed in work and social life. Villages were slowly created by descendants of an original family which gradually spread. Despite the sparse population, societal integrity was large. There were the panigiria (traditional festivals featuring dances, music and consumption of local products), team labor and elder councils who would take the decisions. This unique way of life and architecture was preserved until the end of the 19th century, with many elements surviving until today.

Knights Hospitalier - Ottoman Era
The Knights of St. John, who had their base in Rhodes, exerted some control over Icaria until 1521, when the Ottoman Empire incorporated Icaria into its realm. It was at this time that the problem of piracy reached new heights, where the islanders embraced the tactic of invisibility: they retreated to the island's highlands, hiding their villages and homes. For defence against pirates, aside from this tactic (sparse habitation and hiding of residences) there were watchtowers, various points of concentration and defence (such as plateaus invisible from the sea) and communal hidden supplies to be used in time of need. Their theft was punishable even by death according to the common law of the time. Locals were reported attacking any unwanted visitors on their coastlines, even shipwrecked sailors.

The Icarians lynched the first Turkish tax collector but managed to escape punishment. The oral story in regards to the event talks of an Ottoman Aga, who demanded two locals to carry him on their shoulders atop a seat. The carriers, unable to accept the forcefulness, threw him off a cliff in the Kako Katavasidi area. The Turkish authorities rounded up the population and demanded to know who the perpetrator was, but the answer they received according to legend was "all of us, milord". The Turks realistically determined that there was neither profit nor honour in punishing all.

The Ottomans imposed a very loose administration, not sending any officials to Icaria for several centuries, although in later years they would appoint groups of locals in each village of the island to act as Kodjabashis in order to collect taxes for the empire. The best account that we have of the island during the early years of the Ottoman rule is from the Archbishop J. Georgirenes, who in 1677 described the island as having almost 1,000 hardy, long-lived inhabitants, who were the poorest people in the Aegean.

Without a decent port —the local population destroyed the island's ports long ago to protect themselves from pirate raids— Icaria depended for its very limited trade with the outside world upon small craft that were drawn up on the beaches. Icarian boat-makers had a good reputation for building boats from the island's fir forests. Then they sold boats and lumber for coin and grain in nearby Chios. The inshore waters of the island, as told by Georgirenes, provided the best cockle shellfish in the archipelago. Over the centuries, Ikaria would also become renowned for its charcoal, which became known as Carbon Cariot (Ikarian Charcoal).

Goats and sheep roamed virtually untended in the rocky landscape. Cheeses were made for consumption in every household. Icaria in the 17th century was unusual in the archipelago in not producing any wine for export. The people kept barrels of the wine for their own drinking. They also continued to store it in the old-fashioned way prevalent since the Bronze Age, in terracotta pithoi containers sunk to their rims in earth, thus protecting their supplies from both tax collectors and pirates.

Apart from three small towns, none of which exceeded 100 houses, and numerous village settlements, each house had a walled orchard and a garden plot. Unlike the closely built towns of Samos, the hardy inhabitants lived separately in fortified unfurnished farmsteads.

In 1827, during the Greek War of Independence, Icaria broke away from the Ottoman Empire, but was not included in the narrow territory of the original independent Greece, and it was forced to accept Ottoman rule once more a few years later.

Free State of Icaria

Icaria remained part of the Ottoman Empire until 17 July 1912, when the Icarians expelled the Turkish garrison and thereby achieved independence. After its independence and the outbreak of the First Balkan War, Icaria's sole "warship", the Cleopatra, was used to provide food and supplies to the islands of Samos and Chios, which were captured by the Greek Navy during the war.

George N. Spanos (c. 1872–1912) of Evdilos, killed in a Turkish ambush on 17 July 1912, is honoured as the hero of the Icarian Revolution. His bust, depicting him defiantly, with bandoliers on his body and rifle in hand, may be seen at the memorial established in his honour at the site of his death located in the Icarian town of Chrysostomos. On 18 July 1912, the Free State of Icaria (Ελευθέρα Πολιτεία Ικαρίας, Elefthéra Politía Ikarías) was declared. The neighboring islands of Fournoi Korseon were also liberated and became part of the Free State. Ioannis Malachias (Ιωάννης Μαλαχίας) was the first and only president of the Free State of Icaria.

For five months, it remained an independent country, with its own government, armed forces, national flag, coat of arms, postage stamps, and national anthem. These five months were difficult for the island's economy. There were food shortages and they were at risk of becoming part of the Italian Dodecanese. On 4 November 1912, after a delay due to the Balkan Wars, Icaria officially became part of the Kingdom of Greece. The Ottoman Empire recognized Greece's annexation of Icaria and the other Aegean islands in the Treaty of London (1913).

Second World War
The island suffered losses in property and lives during the Second World War as the result of the Italian and then German occupation. There are no exact figures on how many people starved, but in the village of Karavostamo alone over 100 perished from starvation.

"Red Rock"
After the ravages of the war the nationalists and communists fought in the Greek Civil War (1946–49), and the Greek government used the island to exile about 13,000 communists. To this date, the majority of the locals have remained sympathetic to left parties and communism, and, for this reason, Icaria is referred to by some as the "Red Rock" (Κόκκινος Βράχος, Kokkinos Vrahos).

In his analysis, "Rebels and Radicals; Icaria 1600–2000", historian Anthony J. Papalas (East Carolina University) examines modern Icaria in the light of such 20th-century questions as poverty, emigration to America, the nature of the Axis occupation, the rise of Communism, the Greek Civil War, and the rightwing reaction to radical postwar movements.

Modern era
The quality of life improved greatly after 1960, when the Greek government began to invest in the infrastructure of the island to assist in the promotion of tourism. Today, Icaria is considered one of the world's five "Blue zones" – places where the population regularly lives to an advanced age (one in three make it to their 90s). This is due to healthy diet, lifestyle, and genetics. The Ikaria Study, published in 2011, sought to understand the factors that contributed to longevity. The study also showed the high rate of sexual intercourse among elderly men; 80% of Ikarian males aged between 65 and 100 were found to still be having sex on a regular basis.

Demographics
The inhabitants of the island are known as Icarians or Icariots. (Ικαριότες, Ikariótes).

An Icarian diaspora is found throughout Greece, specifically on Thimena and Fournoi Korseon, as well as in Athens, where a large community is found. The people of Icarian diaspora can be found throughout the world, mainly in Australia, the United States, Canada, Egypt and the United Kingdom.

Icarian Greeks are closely related to other Aegean island Greeks, such as Greeks from Samos, Chios, Fournoi Korseon, and Patmos, as well as Greeks from Anatolia.

Municipality

The present municipality Ikaria was formed in the 2011 local government reform by the merger of the following three former municipalities, that became municipal units:
 * Agios Kirykos
 * Evdilos
 * Raches

Subdivisions
The municipal units Agios Kirykos, Evdilos and Raches are subdivided into the following communities (constituent villages in brackets):

Agios Kirykos
 * Agios Kirykos (Agios Kirykos, Therma Ikarias, Katafygio, Lardades, Mavrato, Koundouma, Mavrikato, Xylosyrtis, Oxea, Tsouredes, Faros)
 * Perdiki (Perdiki, Kioni, Mileopo, Monokampi, Ploumari)
 * Chrysostomos (Chrysostomos, Vardarades, Vaoni, Livadi, Plagia)

Evdilos
 * Kerame, Evdilos, Ikaria.jpgos (Evdilos, Kambos, Agia Kyriaki, Droutsoulas, Kerameio, Kyparissi, Xanthi, Fytema)
 * Arethousa (Arethousa, Kyparissi, Pera Arethousa, Foinikas)
 * Dafni (Dafni, Akamatra, Kosoikia, Petropouli, Steli)
 * Karavostamo
 * Manganitis (Manganitis, Kalamonari)
 * Frantato (Frantato, Avlaki, Kalamourida, Kampos, Kremasti, Maratho, Pigi, Stavlos)

Raches Kato Raches]], Kouniadoi, Mavriannos, Nanouras, Xinta, Proespera, Profitis Ilias, Tsakades)
 * Raches (Christos, Agios Dimitrios, Armenistis, Vrakades, Kares, [[Nas (Ikaria)|Nas or
 * Agios Polykarpos (Agios Polykarpos, Agios Panteleimonas, Gialiskari, Kastanies, Lapsachades, Lomvardades, Mandria)
 * Karkinagri (Karkinagri, Amalo, Kalamos, Lagkada, Pezi, Trapalo)

Museums

Archeological Museum of Kampos The Archaeological Museum, located in the village of Kambos, stands on a hill which was once the ancient fortress of Oinoe, and is immediately next to Agia Irini, Ikaria's oldest church. The museum contains over 250 artifacts, including Neolithic tools, pottery vessels, clay statuettes, columns, coins, and carved headstones.

Archeological Museum of Agios Kirikos Housed in the former lycee of Agios Kirikos, which was built by immigrant Ikarians living in America, the recently renovated neoclassical building dating to 1925 is the home of Ikaria's Archeological Museum. This listed building will house all of Ikaria's most relevant finds and highlight the history and culture of the island in the facilities of a modern museum and research/conservation center.

Complete with multimedia displays and films dedicated to the Myth of Ikaros and the ancient citadel of Drakano, the museum presents Ikaria's archeological findings and relates to the visitor an understanding of the cultural, commercial and social development of the settlements of ancient Ikaria throughout the course of the island's history.

Folk & Historical Museum Of Agios Kirikos Located in Agios Kirikos, The Folk & History Museum of Agios Kirikos in Ikaria was launched in July 2010, and is the result of the long efforts by Professor Themistocles Katsaros. Its mission is to preserve and promote Ikarian folklore, traditions and customs through its display of over 1,500 objects that reflect the history and heritage of Ikaria and its inhabitants. The museum exhibits items of cultural importance from the island, including dresses, textiles, household articles, pottery, agriculture and trade tools & instruments, photos, documents and many other objects.

Of particular interest amongst the items displayed in the museum is the flag of the Free State of Ikaria (1912). Some of the exhibits have been organised thematically and chronologically, so that objects and images give visitors an idea of social and economic life in Ikaria from the 18th century to the 1970s, when traditional life still continued in the region.

Folklore Museum Of Vrakades The Folklore Museum of Vrakades is located in the scenic village of Vrakades, 650 meters above sea level on the north-western side of the island. The village was founded in the 17th century and contains old stone houses and captains' villas of architectural note. The museum houses an interesting collection of items related to the history and people of the region. Of particular interest are documents and memorabilia from the Free State of Ikaria.

Other exhibits include various clay and wooden objects used by housewives, beekeepers, and farmers, ecclesiastical relics from Profit Elias in Vrakades and the convent of Evagelistrias Mavrianou, books by Ikarian writers, Ikarian records and documents over 500 years old. Of note is the cutter, "lanari" in Greek, used for the processing of wool and goat hairs from which the modest local clothing was made, the "lisgos", a simple tool used for making ropes, an old digging tool, and many other tools belonging to the first inhabitants of the island.

Notable people connected with Icaria

 * Eleftheria Arvanitaki (born 1957), singer, originates from Icaria
 * Ioannis Malachias (1880–1958), first and only President of the Free State of Ikaria
 * Aristides Phoutrides (1887–1927), Harvard professor of classical philology
 * Aris Poulianos (born 1924), anthropologist, born in Icaria
 * Zack Space (born 1961), American politician, family originates from Icaria
 * Christodoulos I. Stefanadis (born 1947) professor of cardiology, born on Icaria
 * Christodoulos Xiros (born 1958), Greek terrorist (member of November 17 terrorist group)
 * Anthony Maras, Greek Australian film director
 * Christy Chakos (Chrysostomos Tsakalias), Greek-American artist and sculptor
 * Chris Kourakis, Chief justice of South Australia
 * Mikis Theodorakis, lived in exile on the island
 * Nick Mamatas, American author, family originates from Icaria
 * Yorgos Lanthimos, Greek film director. His grandmother is from Icaria.
 * Elena Carapetis, Australian actress. Her father's family originates in Icaria.
 * Dean Karnazes, American ultramarathon runner and author. His mother's family originates from Icaria.
 * Stephan Pastis, American cartoonist
 * Alex Carapetis, Australian musician
 * Jonathan Carapetis, Australian paediatric physician. His father is from Ikaria.
 * Theo Maras, Greek-Australian property mogul
 * Nik Chapley, Greek-Australian businessman and Foodland owner
 * John Chapley, Greek-Australian businessman and Foodland owner
 * Niki Vasilakis, Greek-Australian violinist
 * George V. Spanos, judge of the California Superior Court, his father was born on Icaria
 * Nicholas Ikaris, sculptor
 * Argyris Tsakalias, Greek public intellectual, theologian, philosopher, radical political activist
 * Elektra Tsakalia, Greek actress (daughter of Argyris)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Icaria


text:
Macropsia

Macropsia is a neurological condition affecting human visual perception, in which objects within an affected section of the visual field appear larger than normal, causing the person to feel smaller than they actually are. Macropsia, along with its opposite condition, micropsia, can be categorized under dysmetropsia. Macropsia is related to other conditions dealing with visual perception, such as aniseikonia and Alice in Wonderland Syndrome (AIWS, also known as Todd's syndrome). Macropsia has a wide range of causes, from prescription and illicit drugs, to migraines and (rarely) complex partial epilepsy, and to different retinal conditions, such as epiretinal membrane. Physiologically, retinal macropsia results from the compression of cones in the eye. It is the compression of receptor distribution that results in greater stimulation and thus a larger perceived image of an object.

Signs and symptoms
The most obvious symptom of macropsia is the presence of exceptionally enlarged objects throughout the visual field. For example, a young girl might see her sister's books as the same size as her sister. Stemming from this symptom, someone with macropsia may feel undersized in relation to his or her surrounding environment. Patients with macropsia have also noted the cessation of auditory function prior to the onset of visual hallucination, indicating possible seizure either before or after the hallucination. A buzzing sound in the ears has also been reported immediately before macropsia development. Some patients claim that symptoms may be eased if an attempt is made to physically touch the object which appears enormous in size. It is important to note, however, that patients typically remain lucid and alert throughout episodes, being able to recount specific details. A person with macropsia may have no psychiatric conditions. Symptoms caused chemically by drugs such as cannabis, magic mushrooms, or cocaine tend to dissipate after the chemical compound has been excreted from the body. Those who acquire macropsia as a symptom of a virus usually experience complete recovery and restoration of normal vision.

Dysmetropsia in one eye, a case of aniseikonia, can present with symptoms such as headaches, asthenopia, reading difficulties, depth perception problems, or double vision. The visual distortion can cause uncorrelated images to stimulate corresponding retinal regions simultaneously impairing fusion of the images. Without suppression of one of the images symptoms from mild poor stereopsis, binocular diplopia and intolerable rivalry can occur.

Psychological effects
There are a broad range of psychological and emotional effects that a person with macropsia may experience. One competing theory has radically stated that macropsia may be an entirely psychological pathological phenomenon without any structural defect or definite cause. They may be in an irritable or angry state, or in contrast, a euphoric state. There is evidence that those who experience Alice in Wonderland Syndrome and associated macropsia are able to recount their experiences with thorough detail. There may be no evidence of psychiatric disturbance and, as a result, no psychiatric therapy may be required. Psychological conditions often arise from macropsia, but the general consensus is that they do not cause macropsia. Those affected may experience extreme anxiety both during and after episodes as a result of the overwhelming nature of his or her distorted visual field. Due to the fear and anxiety associated with the condition, those who have previously had an episode hesitate to recount the episode, although retain the ability to do so. Psychologically, a person with macropsia may feel separation and dissociation from the outside world and even from immediate family. This feeling of dissociation has mostly been noted in child or adolescent patients. The patient may feel that he or she must unfairly contend with hostile and aggressive forces due to the gigantic nature of the surrounding environment. The defense against said forces is usually expressed verbally. The patient may falsely present an outgoing or flamboyant persona, while remaining fearful of people internally. He or she, in an attempt to balance the size distortion, may try to make others feel small in size through insult or hostile behavior. The psychological impact of macropsia on long-time people who have had the condition since childhood may be greater and lead to severe ego-deficiencies. An alternative interpretation of the condition is that macropsia is a response to biophysiological contraction and has no psychological roots. Thus, when a patient reaches for an enlarged object, he or she is overcoming that physiological contraction. However, this theory has been under much scrutiny.

Structural defects
In cases where macropsia affects one eye resulting in differences in the way the two eyes perceive the size or shape of images, the condition is known as aniseikonia. Aniseikonia is known to be associated with certain retinal conditions. Epiretinal membrane has been found to cause metamorphopsia and aniseikonia. Vitreomacular traction caused by the excessive adhesion of vitreous fluid to the retina is related to aniseikonia due to the separation and compression of photoreceptor cells. Macular edema and surgical re-attachment for macula-off rhegmatogenous retinal detachment can also cause an increased separation of macular photoreceptor cells resulting in dysmetropsia. Retinoschisis is another eye disease that has been shown to cause aniseikonia.

There is evidence that a lesion appearing in the posterior area of the ventral occipitotemporal visual pathway can cause macropsia. This lesion can be due to an ischemic cell death after an acute posterior cerebral infarction.

Medications
The most prevalent research on prescription drugs with side effects of macropsia deals with zolpidem and citalopram. Zolpidem is a drug prescribed for insomnia, and although it has proven beneficial effects, there have been numerous reported cases of adverse perceptual reactions. One of these cases discusses an anorexic woman's episode of macropsia, which occurred twenty minutes after taking 10 mg zolpidem. The same woman later had two more episodes of zolpidem-induced macropsia, after taking 5 mg and 2.5 mg zolpidem, respective to each episode. The intensity of the macropsia episodes decreased with the decreasing amount of zolpidem administered; it is implied in the article that the level of intensity was based on the patients accounts of her macropsia episodes, and that no external diagnosis was used. Hoyler points out notable similarities among the different reported cases of zolpidem-induced disorganization. The similarities were that all the cases were reported by women, the disorganization and agitation followed the first administration of zolpidem, and once zolpidem was discontinued, there were no lasting residual effects. It is believed that zolpidem-related macropsia is more prevalent in women because plasma zolpidem concentration is 40% higher in women, a concentration that further increases in anorexic women.

Citalopram-induced macropsia is similar to zolpidem-induced macropsia since both types have been observed in relatively few cases, and neither of the drugs' side effects can be supported by experimental evidence. Citalopram is an antidepressant that inhibits serotonin reuptake. The first case of macropsia thought to be induced by citalopram involves a woman who experienced macropsia after her first administration of 10 mg citalopram. Just as with zolpidem, after the immediate discontinuation of citalopram, there were no further episodes of macropsia.

Illicit drugs
There are suggestions that visual distortions, such as macropsia, can be associated with cocaine use. Episodes of temporary drug-induced macropsia subside as the chemicals leave the body.

Migraine
Past research has linked macropsia to migraine. One of these studies was conducted on Japanese adolescents who reported visual episodic illusions with macropsia and showed that illusions are three times more likely to occur in association with migraine. The illusions were most prevalent among girls between the ages of 16 and 18. It is unlikely that macropsia in Japanese adolescents could be due to epileptic seizure since only 0.3% of Japanese adolescents have epilepsy. No evidence of drugs was found, which eliminates the possibility of the macropsia in the adolescents being drug-induced. It is also unlikely for macropsia in adolescent children to be associated with a serious disease. It is usually the macropsia or other visual disturbance which precedes the painful migrainous headaches. The episodes of macropsia can occur as part of the aura in a migraine. These episodes are often brief, lasting only a few minutes. Adolescents who are deemed to have multiple distortions per episode, such as slow motion vision and macropsia, are even more likely to be people with migraine. The macropsia episodes associated with migraine are typically equivalent to the duration of the aura, which can range from moments to 15 minutes. Non-migrainous headaches are not known to be associated with episodic illusions. Even in the absence of a migraine, a fever or a hypnogogic state can provoke visual illusions, which one might claim to be macropsia. A person with macropsia may fail to see the connection between the migraine and the macropsia, since the conditions may not elicit symptoms at the same time. The pathophysiology of the condition is not fully understood, but the timing of some episodic occurrences with the headaches suggests that there is a connection between macropsia and the vasoconstrictive phase of a migraine. The differences in visual phenomena, such as macropsia with slow motion versus macropsia without slow motion, may result from different areas of the brain being affected by migraine.

Epilepsy
Macropsia may present itself as a symptom of both frontal lobe epilepsy and temporal lobe epilepsy, which may actually help in the diagnosis of those diseases. Children who experience nocturnal hallucinations accompanied by macropsia may seek medical care for panic attack disorders and instead are diagnosed with forms of epilepsy. Epilepsy patients may have no memory of the seizure, but can remember the hallucinations and aura which proceed the attack. Electroencephalography, or EEG imaging, can then be utilized while the patient experiences the episode. It may be subsequently concluded that the EEG is congruent with temporal or frontal lobe seizure. Anxiety and headaches accompany the episodes of visual distortion associated with epilepsy. While Valproic acid has been used to treat this type of seizure, anti-seizure medications appropriate for focal-onset seizures, like oxcarbazapine, have also been used successfully in the treatment of epilepsy-related macropsia.

Hypoglycaemia
Endogenous hypoglycaemia can result in number of visual disturbances and sometimes macropsia. This kind of hypoglycaemia is defined as having an abnormally low blood-sugar level due to anything other than the exogenous administration of insulin. Macropsia has been observed in experimental hypoglycaemia and in patients receiving insulin therapy.

Viruses
Patients with both Epstein-Barr virus and infectious mononucleosis have cited an increase in the sizes of perceived objects, coinciding with other symptoms of Alice in Wonderland Syndrome. Additionally, it has been observed that Epstein-Barr patients who cite hallucinations display abnormal MRI scans. The MRI may show swelling of the cerebral cortex, transient T2 prolongation, and transient lesions. Unlike in MRI's, no abnormalities have been reported in CT scans. It is thus recommended that an Epstein-Barr patient who cites visual hallucinations have an MRI scan. Macropsia may appear either before the onset, or after the resolution, of all clinical symptoms associated with the illness. The duration of the disturbances have been shown to range between two weeks and seven months. Almost all patients with macropsia due to infectious mononucleosis make full recoveries. Patients with Coxsackievirus B1 have reported numerous symptoms of Alice in Wonderland Syndrome, the most common of which being macropsia and micropsia.

Pathophysiology
Macropsia may be a result of optical magnification differences between the eyes, retinal receptor distribution, or the cortical processing of the sampled image. The current hypothesis for the occurrence of dysmetropsia is due to the stretching or compression of the retina leading to the displacement of receptors. Macropsia arises from a compressed receptor distribution leading to a larger perceived image size and conversely, micropsia results from stretching of the retina leading to a more sparse receptor distribution that gives a smaller perceived image size. In the case of macropsia, the greater density of photoreceptor cells leads to greater stimulation making the object seem larger. In some cases, the effects of macropsia have been shown to be field dependent, in that the degree of visual distortion is related to the visual field angle. Non-uniform stretching or compression of the receptor distribution could explain the field dependency of the macropsia. If the compression forces were closer to the fovea the resulting compression would cause a greater amount of macropsia at lower field angles with little effect at higher field angles where the receptor distribution is not as compressed. Alterations in receptor distribution can be the result of epiretinal membrane, neuroretina detachment and/or re-attachment, or retinoschisis. Macropsia caused by surgical re-attachment of macula-off rhegmatogenous retinal detachment is not symmetrical around the fovea, resulting in differences size changes in the horizontal and vertical meridians. Asymmetry has also been observed with retinoschisis, in which macropsia generally results in the vertical direction while micropsia presents in the horizontal direction.

Diagnosis
Macropsia is generally diagnosed once a patient complains of the characteristic symptoms, such as disproportionally large objects in their visual field. The Amsler Grid test can be used to diagnose macropsia, along with other visual maladies depending on the subjective disturbance reported by the patient after looking at the Amsler Grid. Outward bulging of the lines on an Amsler Grid is consistent with patients experiencing macropsisa. The New Aniseikonia Test (NAT) can quantify the degree of macropsia or micropsia independently in the vertical and horizontal meridians. The test consists of red and green semicircles on a black background with a white round fixation target. The size of the red semicircle is held constant while the green semicircle is varied in size in 1% increments. The patient wears a pair of red/green goggles so that one eye is tested at a time, and the patient attempts to determine when the semicircles are the same size. This is termed the reversal threshold and the size difference between the semicircles is reported as the degree of aniseikonia. A positive value indicates that the object was perceived bigger and thus corresponds to macropsia, and conversely a negative value indicates micropsia. The Aniseikonia Inspector contains an aniseikonia test based on the same principles as the NAT, but the test is run on a computer screen, it is based on a forced choice method, and it can measure the size difference as a function of the size of the objects. The functionality of being able to measure the size difference as function of the size (i.e. field dependent testing) is especially important when the macropsia (or micropsia) has a retinal origin.

Treatment
The most common way to treat forms of aniseikonia, including macropsia, is through the use of auxiliary optics to correct for the magnification properties of the eyes. This method includes changing the shape of spectacle lenses, changing the vertex distances with contact lenses, creating a weak telescope system with contact lenses and spectacles, and changing the power of one of the spectacle lenses. Computer software, such as the Aniseikonia Inspector, has been developed to determine the prescription needed to correct for a certain degree of aniseikonia. The problem with correction through optical means is that the optics do not vary with field angle and thus cannot compensate for non-uniform macropsia. Patients have reported significantly improved visual comfort associated with a correction of 5-10% of the aniseikonia.

With regard to drug-induced or virus-induced macropsia, once the underlying problem, either drug abuse or viral infection, is treated, the induced macropsia ceases.

Research
Future research may focus on ways to limit the occurrence of retinally-induced macropsia due to surgery. In terms of treatment, the most effective optical correction is still being researched with respect to visual field angles and direction to a target. The susceptibility of certain age demographics to macropsia is a subject that requires further validation. Overall, there have not been very many reports of macropsia induced by certain drugs, specifically zolpidem and citalopram. Once a larger effort is made to compile such reports, there will inevitably be more research on the subject of macropsia.

title: Macropsia


text:
Cytopathology

Cytopathology (from Greek κύτος, kytos, "a hollow"; πάθος, pathos, "fate, harm"; and -λογία, -logia) is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues. Cytopathology is frequently, less precisely, called "cytology", which means "the study of cells".

Cytopathology is commonly used to investigate diseases involving a wide range of body sites, often to aid in the diagnosis of cancer but also in the diagnosis of some infectious diseases and other inflammatory conditions. For example, a common application of cytopathology is the Pap smear, a screening tool used to detect precancerous cervical lesions that may lead to cervical cancer.

Cytopathologic tests are sometimes called smear tests because the samples may be smeared across a glass microscope slide for subsequent staining and microscopic examination. However, cytology samples may be prepared in other ways, including cytocentrifugation. Different types of smear tests may also be used for cancer diagnosis. In this sense, it is termed a cytologic smear.

Cell collection
There are two methods of collecting cells for cytopathologic analysis: exfoliative cytology, and intervention cytology.

Exfoliative cytology
In this method, cells are collected after they have been either spontaneously shed by the body ("spontaneous exfoliation"), or manually scraped/brushed off of a surface in the body ("mechanical exfoliation"). An example of spontaneous exfoliation is when cells of the pleural cavity or peritoneal cavity are shed into the pleural or peritoneal fluid. This fluid can be collected via various methods for examination. Examples of mechanical exfoliation include Pap smears, where cells are scraped from the cervix with a cervical spatula, or bronchial brushings, where a bronchoscope is inserted into the trachea and used to evaluate a visible lesion by brushing cells from its surface and subjecting them to cytopathologic analysis.

Intervention cytology
In intervention cytology the pathologist intervenes into the body for sample collection.

Fine-needle aspiration
Fine-needle aspiration, or fine-needle aspiration cytology (FNAC), involves use of a needle attached to a syringe to collect cells from lesions or masses in various body organs by microcoring, often with the application of negative pressure (suction) to increase yield. FNAC can be performed under palpation guidance (i.e., the clinician can feel the lesion) on a mass in superficial regions like the neck, thyroid or breast; FNAC may be assisted by ultrasound or CAT scan for sampling of deep-seated lesions within the body that cannot be localized via palpation. FNAC is widely used in many countries, but success rate is dependent on the skill of the practitioner. If performed by a pathologist alone, or as team with pathologist-cytotechnologist, the success rate of proper diagnosis is higher than when performed by a non-pathologist. This may be due to the pathologist's ability to immediately evaluate specimens under a microscope and immediately repeat the procedure if sampling was inadequate.

Fine needles are 23 to 27 gauge. Because needles as small as 27 gauge can almost always yield diagnostic material, FNAC is often the least injurious way to obtain diagnostic tissue from a lesion. Sometimes a syringe holder may be used to facilitate using one hand to perform the biopsy while the other hand is immobilizing the mass. Imaging equipment such as a CT scanner or ultrasound may be used to assist in locating the region to be biopsied.

FNAC has become synonymous to interventional cytology.

Sediment cytology
For cytology of sediment, the sample is collected from the fixative that was used for processing the biopsy or autopsy specimen. The fixative is mixed properly and taken into a centrifuge tube and is centrifuged. The sediment is used for smearing. These sediments are the cells that are shed by the autopsy and biopsy specimen during processing.

Imprint cytology
Imprint cytology is a preparation wherein the tissue of interest touches a glass slide, leaving behind its imprint in the form of cells on the slide. The imprint can subsequently be stained and studied.

Preparation
After sampling, two main techniques for processing are used:
 * Smearing of sample directly onto a glass slide.
 * Liquid-based cytology. With the latter, the sample is placed in a liquid that is then processed for further investigation.

Processing of specimens may result in visual artifacts:

For better visualization of cells and their components, specimens are inked, such as by the Papanicolaou stain, or Romanowsky stain derivatives which include Giemsa, Jenner, Wright, Field, May–Grünwald and Leishman stains.

Parameters
The nucleus of the cell is very important in evaluating the cellular sample. In cancerous cells, altered DNA activity can be seen as a physical change in the nuclear qualities. Since more DNA is unfolded and being expressed, the nucleus will be darker and less uniform, larger than in normal cells, and often show a bright-red nucleolus.

While the cytologist's primary responsibility is to discern whether cancerous or precancerous pathology is present in the cellular sample analysed, other pathologies may be seen such as:
 * microbial infections: parasitic, viral, and/or bacterial
 * reactive changes
 * immune reactions
 * cell aging
 * amyloidosis
 * autoimmune diseases

Various normal functions of cell growth, metabolism, and division can fail or work in abnormal ways and lead to diseases.

Cytopathology is best used as one of three tools, the second and third being the physical examination and medical imaging. Cytology can be used to diagnose a condition and spare a patient from surgery to obtain a larger specimen. An example is thyroid FNAC; many benign conditions can be diagnosed with a superficial biopsy and the patient can go back to normal activities right away. If a malignant condition is diagnosed, the patient may be able to start radiation/chemotherapy, or may need to have surgery to remove and/or stage the cancer.

Some tumors may be difficult to biopsy, such as sarcomas. Other rare tumors may be dangerous to biopsy, such as pheochromocytoma. In general, a fine-needle aspiration can be done anywhere it is safe to put a needle, including liver, lung, kidney, and superficial masses.

Proper cytopathology technique takes time to master. Cytotechnologists and cytopathologists can assist clinicians by assisting with sample collection. A "quick read" is a peek under the microscope and can tell the clinician whether enough diagnostic material was obtained. Cytological specimens must be properly prepared so that the cells are not damaged.

Further information about the specimen may be gained by immunohistochemical stains and molecular testing, particularly if the sample is prepared using liquid based cytology. Often "reflex" testing is performed, such as HPV testing on an abnormal pap test or flow cytometry on a lymphoma specimen.

Body regions
Cytopathologic techniques are used in the examination of virtually all body organs and tissues:
 * Gynecologic cytology – concerning the female reproductive tract
 * Urinary tract cytology – concerning the ureters, urinary bladder and urethra. See Urine cytology.
 * Effusion cytology – concerning fluids collections, especially within the peritoneum, pleura and pericardium
 * Breast cytology – principally concerning the female breast
 * Vaginal cytology - principally concerning non-human mammals
 * Thyroid cytology – concerning the thyroid gland
 * Lymph node cytology – concerning lymph nodes
 * Respiratory cytology – concerning the lungs and airways
 * Gastrointestinal cytology – concerning the alimentary tract
 * Soft tissue, bone and skin cytology
 * Kidney and adrenal cytology
 * Liver and pancreas cytology
 * Central nervous system cytology
 * Eye cytology
 * Salivary gland cytology

title: Cytopathology