Angle-closure glaucoma has been described in association with metabolic or ocular disorders like cystinosis and nanophthalmos. Nanophthalmos is a rare, bilateral and sight threatening disease characterized by hyperopia, short axial length, small corneal diameter, thickened sclera, shallow anterior chamber and narrow angle [4
]. Patients with nanophthalmos have risk for developing angle-closure glaucoma by the fourth to sixth decade of life due to the progressive shallowing of the anterior chamber and narrowing of the angle [5
]. Posterior pushing mechanism leading to pupillary block and peripheral anterior synechiae formation is the most common cause of angle closure glaucoma in nanophthalmic eyes.
Cystinosis is a rare autosomal recessive metabolic disorder characterized by intracellular accumulation of cystine, the disulfide of amino acid cysteine [6
]. The responsible gene, CTNS, encodes cystinosin, that transports cystine out of the lysosome [7
]. As a result of deficient or absent cystinosin, cystine accumulates within lysosomes and forms crystals in many tissuses, such as kidneys, bone marrow, pancreas, muscle, brain and eye [6
]. Based on the age at onset and severity of the symptoms, three clinical forms of cystinosis including infantile nephropathic cystinosis, intermediate cystinosis and ocular cystinosis were described [8
]. Ocular cystinosis presents only with ophthalmic symptoms and never exhibit systemic manifestations [6
]. Patients with nephropathic cystinosis have leukocyte cystine levels of 5 to 23
nmol of half-cystine/milligram of protein, whereas patients with ocular cystinosis have values of 1 to 3
nmol of half-cystine/milligram of protein [6
]. Our patient did not display any systemic abnormalities and leukocyte cystine level (1.1
nmol half-cystine/mg protein ) was consistent with ocular cystinosis.
The glaucoma may be the result of angle closure with pupillary block due to posterior synechiae in cystinosis patients. Iris, ciliary body or angle abnormalities may also contribute to the development of glaucoma in patients with cystinosis [9
]. Mungan et al. [9
] reported of ocular UBM findings which revealed the ciliary body configuration similar to the findings in plateau iris in patients with cystinosis. They did not observe any evidence of increased iris thickness, posterior synechiae, or anterior iris bowing. However, in the present study, UBM revealed 360 degrees circumferential narrowing of angle without an evidence of plateau iris-
like configuration and uveal effusion in both eyes. In addition, gonioscopy revealed an extremely narrow angle with peripheral anterior synechiae occupying approximately 50% of each angle.
Crystal accumulation in the conjunctiva and cornea, and pigmentary retinopathy are originally the most commonly described ophthalmic manifestations of cystinosis. Although patients with ocular cystinosis do not exhibit a retinal pigment abnormality, posterior segment involvement associated with retinal degeneration have been described in infantile nephropathic cystinosis [10
]. The most common retinal finding in these eyes was patches of depigmentation in the periphery with pigmentary mottling [10
]. However, in the present study, areas of stippled and punctate hypopigmentation of RPE without the presence of hiperpigmentation were observed at posterior pole and around the optic disc. Electrophysiological evaluation revealed a cone-
rod pattern of retinal dysfunction. Our patient exhibited localized foveal schisis demonstrated by OCT. Similar retinal findings have been described in association with nanophtalmos [2
]. Zenteno et al. [2
] showed alterations of the RPE with cystic changes very similar to those described in our patients in their study and they described the clinical feature of a new syndrome presenting with nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen. While not noted in their patients, angle closure glaucoma and ocular cystinosis were observed in our case. However, optic disc drusen was not detected in our patient.
In conclusion, this case report brings into discussion a new clinical entity of angle closure glaucoma in nanophthalmia accompanied by ocular cystinosis-foveoschisis-pigmentary retinal dystrophy complex. Further study of additional subjects with this complex would help to clarify whether these disorders is simply an unusual coexistence of unrelated pathologies or a new and distinct pathological entity.