No particular risk factors have been conclusively identified; however, there have been a few reports that demonstrate an autosomal dominant pattern of inheritance in some families. Therefore, a family history of optic pits may be a possible risk factor.

Optic pits occur equally between men and women. They are seen in roughly 1 in 10,000 eyes, and approximately 85% of optic pits are found to be unilateral (i.e. in only one eye of any affected individual). About 70% are found on the temporal side (or lateral one-half) of the optic disc. Another 20% are found centrally, while the remaining pits are located either superiorly (in the upper one-half), inferiorly (in the lower one-half), or nasally (in the medial one-half towards the nose).

It is estimated that this much less common form of retinoschisis affects one in 5,000 to 25,000 individuals, primarily young males. "Schisis" is derived from the Greek word meaning "splitting", describing the splitting of the retinal layers from each other. However, "schisis" is a word fragment, and the term "retinoschisis" should be used, as should the term "iridoschisis" when describing splitting of the iris. If the retinoschisis involves the macula, then the high-resolution central area of vision used to view detail is lost, and this one form of macular disease. Although it might be described by some as a "degeneration", the term "macular degeneration" should be reserved for the specific disease "age-related macular degeneration".

Retinoschisis can be caused by an X-linked genetic defect, affecting the vision of men who inherit the disease from their unaffected carrier mothers. The genetic form of this disease usually starts during childhood and is called X-linked Juvenile Retinoschisis (XLRS) or Congenital Retinoschisis. Affected males are usually identified in grade school, but occasionally are identified as young infants.

Very few affected individuals go completely blind from retinoschisis, but some sufferers have very limited reading vision and are "legally blind". Visual acuity can be reduced to less than 20/200 in both eyes. Individuals affected by XLRS are at an increased risk for retinal detachment and eye hemorrhage, among other potential complications.

Retinoschisis causes acuity loss in the center of the visual field through the formation of tiny cysts in the retina, often forming a "spoke-wheel" pattern that can be very subtle. The cysts are usually only detectable by a trained clinician. In some cases vision cannot be improved by glasses, as the nerve tissue itself is damaged by these cysts.

The National Eye Institute (NEI) of the National Institutes of Health (NIH) is currently conducting clinical and genetic studies of X-Linked Juvenile Retinoschisis. This study is currently recruiting patients. A better understanding of why and how XLRS develops might lead to improved treatments. Males diagnosed with X-linked juvenile retinoschisis and females who are suspected carriers may be eligible to participate. In addition to giving a medical history and submitting medical records, participants submit a blood sample and the NEI will perform a genetic analysis. There is no cost to participate in this study.

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.

Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel (or simply vitreous) of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an adhesion, this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological vitreomacular traction (VMT) can cause severe ocular damage.

The current standard of care for treating these adhesions is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye. A biological agent for non-invasive treatment of adhesions called ocriplasmin has been approved by the FDA on Oct 17 2012.

Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion, and diabetic retinopathy (DR).

The causes of macular edema are numerous and different causes may be inter-related.

- It is commonly associated with diabetes. Chronic or uncontrolled diabetes type 2 can affect peripheral blood vessels including those of the retina which may leak fluid, blood and occasionally fats into the retina causing it to swell.

- Age-related macular degeneration may cause macular edema. As individuals age there may be a natural deterioration in the macula which can lead to the depositing of drusen under the retina sometimes with the formation of abnormal blood vessels.

- Replacement of the lens as treatment for cataract can cause pseudophakic macular edema. (‘pseudophakia’ means ‘replacement lens’) also known as Irvine-Gass syndrome The surgery involved sometimes irritates the retina (and other parts of the eye) causing the capillaries in the retina to dilate and leak fluid into the retina. Less common today with modern lens replacement techniques.

- Chronic uveitis and intermediate uveitis can be a cause.

- Blockage of a vein in the retina can cause engorgement of the other retinal veins causing them to leak fluid under or into the retina. The blockage may be caused, among other things, by atherosclerosis, high blood pressure and glaucoma.

- A number of drugs can cause changes in the retina that can lead to macular edema. The effect of each drug is variable and some drugs have a lesser role in causation. The principal medication known to affect the retina are:- latanoprost, epinephrine, rosiglitazone, timolol and thiazolidinediones among others.

- A few congenital diseases are known to be associated with macular edema for example retinitis pigmentosa and retinoschisis.

Cystoid macular edema (CME) involves fluid accumulation in the outer plexiform layer secondary to abnormal perifoveal retinal capillary permeability. The edema is termed "cystoid" as it appears cystic; however, lacking an epithelial coating, it is not truly cystic. The cause for CME can be remembered with the mnemonic "DEPRIVEN" (diabetes, epinepherine, pars planitis, retinitis pigmentosa, Irvine-Gass syndrome, venous occlusion, E2-prostaglandin analogues, nicotinic acid/niacin).

Diabetic macular edema (DME) is similarly caused by leaking macular capillaries. DME is the most common cause of visual loss in both proliferative, and non-proliferative diabetic retinopathy.

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-of 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 occippitotemporal visual pathway can cause macropsia. This lesion can be due to an ischemic cell death after an acute posterior cerebral infarction.

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.