A diagnosis of choroideremia can be made based on family history, symptoms, and the characteristic appearance of the fundus. However, choroideremia shares several clinical features with retinitis pigmentosa, a similar but broader group of retinal degenerative diseases, making a specific diagnosis difficult without genetic testing. Because of this choroideremia is often initially misdiagnosed as retinitis pigmentosa. A variety of different genetic testing techniques can be used to make a differential diagnosis.

The extent of retinal damage is assessed by fluorescent angiography, retinal scanning and optical coherence tomography; electrophysiological examinations such as electroretinography (ERG) or multifocal electroretinography (mfERG) may also be used.

An accurate diagnosis of retinitis pigmentosa relies on the documentation of the progressive loss photoreceptor cell function, confirmed by a combination of visual field and visual acuity tests, fundus and optical coherence imagery, and electroretinography (ERG),

Visual field and acuity tests measure and compare the size of the patient's field of vision and the clarity of their visual perception with the standard visual measurements associated with healthy 20/20 vision. Clinical diagnostic features indicative of retinitis pigmentosa include a substantially small and progressively decreasing visual area in the visual field test, and compromised levels of clarity measured during the visual acuity test. Additionally, optical tomography such as fundus and retinal (optical coherence) imagery provide further diagnostic tools when determining an RP diagnosis. Photographing the back of the dilated eye allows the confirmation of bone spicule accumulation in the fundus, which presents during the later stages of RP retinal degeneration. Combined with cross-sectional imagery of optical coherence tomography, which provides clues into photoreceptor thickness, retinal layer morphology, and retinal pigment epithelium physiology, fundus imagery can help determine the state of RP progression.

While visual field and acuity test results combined with retinal imagery support the diagnosis of retinitis pigmentosa, additional testing is necessary to confirm other pathological features of this disease. Electroretinography (ERG) confirms the RP diagnosis by evaluating functional aspects associated with photoreceptor degeneration, and can detect physiological abnormalities before the initial manifestation of symptoms. An electrode lens is applied to the eye as photoreceptor response to varying degrees of quick light pulses is measured. Patients exhibiting the retinitis pigmentosa phenotype would show decreased or delayed electrical response in the rod photoreceptors, as well as possibly compromised cone photoreceptor cell response.

The patient's family history is also considered when determining a diagnosis due to the genetic mode of inheritance of retinitis pigmentosa. At least 35 different genes or loci are known to cause "nonsyndromic RP" (RP that is not the result of another disease or part of a wider syndrome). Indications of the RP mutation type can be determine through DNA testing, which is available on a clinical basis for:

- (autosomal recessive, Bothnia type RP)

- (autosomal dominant, RP1)

- (autosomal dominant, RP4)

- (autosomal dominant, RP7)

- (autosomal dominant, RP13)

- (autosomal dominant, RP18)

- CRB1 (autosomal recessive, RP12)

- (autosomal recessive, RP19)

- (autosomal recessive, RP20)

For all other genes (e.g. DHDDS), molecular genetic testing is available on a research basis only.

RP can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. X-linked RP can be either recessive, affecting primarily only males, or dominant, affecting both males and females, although males are usually more mildly affected. Some digenic (controlled by two genes) and mitochondrial forms have also been described.

Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing.

Anomalies of the hair shaft caused by ectodermal dysplasia should be ruled out. Mutations in the CDH3 gene can also appear in EEM syndrome.

The fundus exam via ophthalmoscopy is essentially normal early on in cone dystrophy, and definite macular changes usually occur well after visual loss. Fluorescein angiography (FA) is a useful adjunct in the workup of someone suspected to have cone dystrophy, as it may detect early changes in the retina that are too subtle to be seen by ophthalmoscope. For example, FA may reveal areas of hyperfluorescence, indicating that the RPE has lost some of its integrity, allowing the underlying fluorescence from the choroid to be more visible. These early changes are usually not detected during the ophthalmoscopic exam.

The most common type of macular lesion seen during ophthalmoscopic examination has a bull’s-eye appearance and consists of a doughnut-like zone of atrophic pigment epithelium surrounding a central darker area. In another, less frequent form of cone dystrophy there is rather diffuse atrophy of the posterior pole with spotty pigment clumping in the macular area. Rarely, atrophy of the choriocapillaris and larger choroidal vessels is seen in patients at an early stage. The inclusion of fluorescein angiography in the workup of these patients is important since it can help detect many of these characteristic ophthalmoscopic features. In addition to the retinal findings, temporal pallor of the optic disc is commonly observed.

As expected, visual field testing in cone dystrophy usually reveals a central scotoma. In cases with the typical bull’s-eye appearance, there is often relative central sparing.

Because of the wide spectrum of fundus changes and the difficulty in making the diagnosis in the early stages, electroretinography (ERG) remains the best test for making the diagnosis. Abnormal cone function on the ERG is indicated by a reduced single-flash and flicker response when the test is carried out in a well-lit room (photopic ERG). The relative sparing of rod function in cone dystrophy is evidenced by a normal scotopic ERG, i.e. when the test is carried out in the dark. In more severe or longer standing cases, the dystrophy involves a greater proportion of rods with resultant subnormal scotopic records. Since cone dystrophy is hereditary and can be asymptomatic early on in the disease process, ERG is an invaluable tool in the early diagnosis of patients with positive family histories.

Cone dystrophy in general usually occurs sporadically. Hereditary forms are usually autosomal dominant, and instances of autosomal recessive and X-linked inheritance also occur.

In the differential diagnosis, other macular dystrophies as well as the hereditary optic atrophies must be considered. Fluorescent angiography, ERG, and color vision tests are important tools to help facilitate diagnosis in early stages.

The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.

Stargardt disease has no impact on general health and life expectancy is normal. Some patients, usually those with the late onset form, can maintain excellent visual acuities for extended periods, and are therefore able to perform tasks such as reading or driving.

While nothing currently can be done to stop or reverse the retinal degeneration, there are steps that can be taken to slow the rate of vision loss. UV-blocking sunglasses for outdoors, appropriate dietary intake of fresh fruit and leafy green vegetables, antioxidant vitamin supplements, and regular intake of dietary omega-3 very-long-chain fatty acids are all recommended.

One study found that a dietary supplement of lutein increases macular pigment levels in patients with choroideremia. Over a long period of time, these elevated levels of pigmentation could slow retinal degeneration. Additional interventions that may be needed include surgical correction of retinal detachment and cataracts, low vision services, and counseling to help cope with depression, loss of independence, and anxiety over job loss.

STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.

Retinitis pigmentosa is the leading cause of inherited blindness, with approximately 1/4,000 individuals experiencing the non-syndromic form of their disease within their lifetime. It is estimated that 1.5 million people worldwide are currently affected. Early onset RP occurs within the first few years of life and is typically associated with syndromic disease forms, while late onset RP emerges from early to mid-adulthood.

Autosomal dominant and recessive forms of retinitis pigmentosa affect both male and female populations equally; however, the less frequent X-linked form of the disease affects male recipients of the X-linked mutation, while females usually remain unaffected carriers of the RP trait. The X-linked forms of the disease are considered severe, and typically lead to complete blindness during later stages. In rare occasions, a dominant form of the X-linked gene mutation will affect both males and females equally.

Due to the genetic inheritance patterns of RP, many isolate populations exhibit higher disease frequencies or increased prevalence of a specific RP mutation. Pre-existing or emerging mutations that contribute to rod photoreceptor degeneration in retinitis pigmentosa are passed down through familial lines; thus, allowing certain RP cases to be concentrated to specific geographical regions with an ancestral history of the disease. Several hereditary studies have been performed to determine the varying prevalence rates in Maine (USA), Birmingham (England), Switzerland (affects 1/7000), Denmark (affects 1/2500), and Norway. Navajo Indians display an elevated rate of RP inheritance as well, which is estimated as affecting 1 in 1878 individuals. Despite the increased frequency of RP within specific familial lines, the disease is considered non-discriminatory and tends to equally affect all world populations.

Though there is no treatment for Cone dystrophy, certain supplements may help in delaying the progression of the disease.

The beta-carotenoids, lutein and zeaxanthin, have been evidenced to reduce the risk of developing age related macular degeneration (AMD), and may therefore provide similar benefits to Cone dystrophy sufferers.

Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early AMD, and in conjunction with low glycemic index foods, with reduced progression of advanced AMD, and may therefore delay the progression of cone dystrophy.

This may be present in conditions causing traction on the retina especially at the macula. This may occur in:

a) The vitreomacular traction syndrome; b) Proliferative diabetic retinopathy with vitreoretinal traction; c) Atypical cases of impending macular hole.

Fluorescein angiography is usually performed for diagnosis and follow-up of patients with POHS.

Usually being asymptomatic, drusen are typically found during routine eye exams where the pupils have been dilated.

Macular telangiectasia type 1 must be differentiated from secondary telangiectasis caused by retinal vascular diseases such as retinal venous occlusions, diabetic retinopathy, radiation retinopathy, sickle cell maculopathy, inflammatory retinopathy/Irvine–Gass syndrome, ocular ischemic syndrome/carotid artery obstruction, hypertensive retinopathy, polycythemia vera retinopathy, and localized retinal capillary hemangioma. In addition, Macular telangiectasia type 1 should be clearly differentiated from dilated perifoveal capillaries with evidence of vitreous cellular infiltration secondary to acquired inflammatory disease or tapetoretinal dystrophy. Less commonly, macular telangiectasis has been described in association with fascioscapulohumeral muscular dystrophy, incontinentia pigmenti, and familial exudative vitreoretinopathy with posterior pole involvement.

Macular telangiectasia type 2 is commonly under-diagnosed. The findings may appear very similar to diabetic retinopathy, and many cases ave been incorrectly ascribed to diabetic retinopathy or age-related macular degeneration. Recognition of this condition can save an affected patient from unnecessarily undergoing extensive medical testing and/or treatment. MacTel should be considered in cases of mild paramacular dot and blot hemorrhages and in cases of macular and paramacular RPE hyperplasia where no other cause can be identified.

Treatment is based

on the stage of the disease. Stage 1 does not

require treatment and

should be observed. 4

Neovascularization

(stage 2) responds well

to laser ablation or

cryotherapy.2,4 Eyes

with retinal detachments (stages

3 through 5) require surgery, with

earlier stages requiring scleral

buckles and later stages ultimately

needing vitrectomy. 2,4

More recently, the efficacy of

anti-VEGF intravitreal injections

has been studied. In one study,

these injections, as an in adjunct

with laser, helped early stages

achieve stabilization, but further

investigation is needed.6

Retinoschisis involving the central part of the retina secondary to an optic disc pit was erroneously considered to be a serous retinal detachment until correctly described by Lincoff as retinoschisis. Significant visual loss may occur and following a period of observation for spontaneous resolution, treatment with temporal peripapillary laser photocoagulation followed by vitrectomy and gas injection followed by face-down positioning is very effective in treating this condition.

FEVR is, as its name suggests,

familial and can be inherited in an

autosomal dominant, autosomal

recessive or X-linked recessive pattern.1-3 It is caused by mutations in

FZD4, LRP5, TSPAN12 and NDP

genes, which impact the wingless/

integrated (Wnt) receptor signaling

pathway. 3 Disruption of this path

way leads to abnormalities of vascu-

lar growth in the peripheral retina. 2,3

It is typically bilateral, but asymmetric, with varying degrees of

progression over the individual’s

lifetime. Age of onset varies, and

visual outcome can be strongly

influenced by this factor. Patients

with onset before age three have a

more guarded long-term prognosis

whereas those with later onset are

more likely to have asymmetric

presentation with deterioration of

vision in one eye only. 2-3 However,

because FEVR is a lifelong disease,

these patients are at risk even as

adults.2 Ocular findings and useful

vision typically remain stable if the

patient does not have deterioration

before age 20.2,4 Due to the variability and unpredictability of the

disease course, patients with FEVR

should be followed throughout

their lifetime.

Clinical presentation can vary

greatly. In mild variations, patients

may experience peripheral vascular

changes, such as peripheral avascular zone, vitreoretinal adhesions,

arteriovenous anastomoses and a

V-shaped area of retinochoroidal

degeneration. 4 Severe forms may

present with neovascularization,

subretinal and intraretinal hemorrhages and exudation. 4 Neovascularization is a poor prognostic

indicator and can lead to retinal

folds, macular ectopia and tractional retinal detachment. 2,4 Widefield FA has been crucial in

helping to understand this disease,

as well as helping to confirm the

diagnosis. An abrupt cessation

of the retinal capillary network

in a scalloped edge posterior to

fibrovascular proliferations can

be made using FA.2,3,5 Patients can

also show delayed transit filling on

FA as well as delayed/patchy choroidal filling, bulbous vascular terminals, capillary dropout, venous/venous shunting and abnormal

branching patterns. 2,3,5 The staging of FEVR is similar

to that of retinopathy of prematurity. The first two stages involve an

avascular retinal periphery with or

without extraretinal vascularization (stage 1 and 2, respectively). 4 Stages three through five delineate

levels of retinal detachment; stage 3

is subtotal without foveal involvement, stage 4 is subtotal with foveal

involvement and stage 5 is a total

detachment, open or closed funnel.4

Because there was neovascularization in the absence of retinal detachment, our patient was

considered to have

stage 2.

Diagnosis of age-related macular degeneration rests on signs in the macula, irrespective of visual acuity. Diagnosis of AMD may include the following procedures and tests:

- The transition from dry to wet AMD can happen rapidly, and if it is left untreated can lead to legal blindness in as little as six months. To prevent this from occurring and to initiate preventative strategies earlier in the disease process, dark adaptation testing may be performed. A dark adaptometer can detect subclinical AMD at least three years earlier than it is clinically evident.

- There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss in contrast sensitivity can be quickly and easily measured by a contrast sensitivity test like Pelli Robson performed either at home or by an eye specialist.

- When viewing an Amsler grid, some straight lines appear wavy and some patches appear blank

- When viewing a Snellen chart, at least 2 lines decline

- Preferential hyperacuity perimetry changes (for wet AMD)

- In dry macular degeneration, which occurs in 85–90 percent of AMD cases, drusen spots can be seen in Fundus photography

- In wet macular degeneration, angiography can visualize the leakage of bloodstream behind the macula. Fluorescein angiography allows for the identification and localization of abnormal vascular processes.

- Using an electroretinogram, points in the macula with a weak or absent response compared to a normal eye may be found

- Farnsworth-Munsell 100 hue test and Maximum Color Contrast Sensitivity test (MCCS) for assessing color acuity and color contrast sensitivity

- Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the follow-up evaluation of the response to treatment with antiangiogenic drugs.

Optic pits should be diagnosed by an eye care professional who can perform a thorough exam of the back of the eye using an ophthalmoscope.

More recently, the development of a special technology called optical coherence tomography (OCT) has allowed better visualization of the retinal layers. It has been used to demonstrate a marked reduction in the thickness of the retinal nerve fiber layer in the quadrant corresponding to the optic pit. This is not yet in standard use for diagnosis of an optic pit, but may be helpful in supporting a diagnosis.

Although MacTel is uncommon, its prevalence is probably higher than most physicians believe. The early findings are subtle, so the diagnosis is likely often missed by optometrists and general ophthalmologists. MacTel was detected in 0.1% of subjects in the Beaver Dam study population over age 45 years, but this is probably an underestimate because identification was made based only on color photographs.

No major new biomicroscopic features of MacTel have been identified since the early work of Gass and colleagues.

The advent of optical coherence tomography (OCT) has allowed better characterization of the nature of the inner and outer lamellar cavities. Loss of central masking seen on autofluorescence studies, apparently due to loss of luteal pigment, is now recognized as probably the earliest and most sensitive and specific MacTel abnormality.

The key fundus findings in macular telangiectasia type 2 involve retinal crystalline—fine, refractile deposits in the superficial retinal layers—may be seen within the affected area.a focal area of diminished retinal transparency (i.e. "greying") and/or small retinal hemorrhages just temporal to the fovea. Dilated capillaries may also be noted within this area, and while this is often difficult to visualize ophthalmoscopically, the abnormal capillary pattern is readily identifiable with fluorescein angiography.

Areas of focal RPE hyperplasia, i.e.pigment plaques, often develop in the paramacular region as a response to these abnormal vessels. Other signs of macular telangiectasia type 2 include right angle venules, representing an unusual alteration of the vasculature in the paramacular area, with vessels taking an abrupt turn toward the macula as if being dragged.

Diagnosis of MacTel type 2 may be aided by the use of advanced imaging techniques such as fluorescein angiography, fundus autofluorescence, and OCT. These can help to identify the abnormal vessels, pigment plaques, retinal crystals, foveal atrophy and intraretinal cavities associated with this disorder.

Fluorescein angiography (FA) is helpful in identifying the anomalous vasculature, particularly in the early stages of Type 2 disease. Formerly, FA was essential in making a definitive diagnosis. However, the diagnosis can be established with less invasive imaging techniques such as OCT and fundus autofluorescence. Some clinicians argue that FA testing may be unnecessary when a diagnosis is apparent via less invasive means.

The natural history of macular telangiectasia suggests a slowly progressive disorder. A retrospective series of 20 patients over 10 to 21 years showed deterioration of vision in more than 84% of eyes, either due to intra-retinal edema and serous retinal detachment (Type 1) or pigmented RPE scar formation or neovascularisation (Type 2).

Diagnosis of PIC can be difficult because the appearance may be similar to other conditions and types of posterior uveitis, especially other forms of the so called white dot syndromes. The diagnosis is made by eliminating all the other possibilities by careful examination by an experienced ophthalmologist, aided with visual field testing and Fluorescein angiography (an intra-venous dye used to show the blood vessels at the back of the eye).

It is important that the correct diagnosis is made because treatment may be quite different for apparently similar conditions.

A practical application of AMD-associated genetic markers is in the prediction of progression of AMD from early stages of the disease to neovascularization.

Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. The retinal pigment epithelium also degenerates. Over time, the abnormal accumulation of this substance can damage the cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision and may experience blurry or distorted vision, and loss is rarely symmetric. Scotomata appear, first with red light and then for green; finally, relative (or in more serious cases, absolute) scotomata occur with white light. Vitelliform macular dystrophy does not affect side (peripheral) vision or the ability to see at night.

Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; however, the onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in middle age, and tends to cause relatively mild vision loss. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination.

Patients with optic disc drusen should be monitored periodically for ophthalmoscopy, Snellen acuity, contrast sensitivity, color vision, intraocular pressure and threshold visual fields. For those with visual field defects optical coherence tomography has been recommended for follow up of nerve fiber layer thickness. Associated conditions such as angioid streaks and retinitis pigmentosa should be screened for. Both the severity of optic disc drusen and the degree of intraocular pressure elevation have been associated with visual field loss. There is no widely accepted treatment for ODD, although some clinicians will prescribe eye drops designed to decrease the intra-ocular pressure and theoretically relieve mechanical stress on fibers of the optic disc. Rarely choroidal neovascular membranes may develop adjacent to the optic disc threatening bleeding and retinal scarring. Laser treatment or photodynamic therapy or other evolving therapies may prevent this complication.

Laser treatment of drusen has been studied. While it is possible to eliminate drusen with this treatment strategy, it has been shown that this fails to reduce the risk of developing the choroidal neovascularisation which causes the blindness associated with age-related macular degeneration.