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The exact prevalence of nanophthalmos is unknown but is likely to be below 1/2,000. However, the prevalence is higher among consanguineous populations.

The disease occurs neonatally or during infancy. Typical clinical signs include an axial length inferior to 20 mm, a lens/eye ratio 4 to 8 times greater than normal, thickened and abnormally dense sclera, a thickened lens and choroids, and severe hyperopia (+7.00 D to +13.00 D). Despite its small size, the functionality and organization of the eye are preserved. Nanophthalmos is generally bilateral. Strabismus is present in most patients. The association of nanophthalmos and pigmentary retinopathy or Best disease has been reported. The condition can be simple (occurring in isolation), complex (associated with other malformations such as colobomas, anterior segment dysgenesis, and lens and posterior segment abnormalities) or syndromic (as part of a rare syndrome).

To date, five genes have been associated with the disease : MFRP (11q23.3, coding for a frizzled protein playing a role in the regulation of cell growth, differentiation and polarity during development), TMEM98 (17q11.2, coding for an ubiquitous protein which could be involved in the scleral pathologic thickening and secondary glaucoma development in the disease), PRSS56 (2q37.1, the exact physiopathological mechanism is unknown), BEST1 (11q12.3, involved for example in the development of angle-closure glaucoma) and CRB1 (1q31.3, coding for a protein essential for the neuronal development of the retina). Other loci are also associated with nanophthalmos.

Diagnosis is based on clinical findings and ophthalmologic examinations involving ocular biometry, ultrasonography, as well as corneal diameter and intraocular pressure measurements.

Nanophthalmos should be differentiated from posterior microphthalmos.

The disease may be inherited as an autosomal dominant or recessive trait. It can also occur sporadically.

Treatment may include surgery (iridotomy, iridoplasty, glaucoma filtering surgery, and lens extraction), but side effects (malignant glaucoma, uveal effusion, nonrhegmatogenous retinal detachment and expulsive hemorrhage) may occur. Complications can be prevented by performing a sclerectomy before any intraocular intervention.

Angle-closure glaucoma is a constant finding in patients with nanophthalmia but the prognosis is favorable if this manifestation is correctly managed.