Exome-based investigation of the genetic basis of human pigmentary glaucoma

Background Glaucoma is a leading cause of visual disability and blindness. Release of iris pigment within the eye, pigment dispersion syndrome (PDS), can lead to one type of glaucoma known as pigmentary glaucoma. PDS has a genetic component, however, the genes involved with this condition are largely unknown. We sought to discover genes that cause PDS by testing cohorts of patients and controls for mutations using a tiered analysis of exome data. Results Our primary analysis evaluated melanosome-related genes that cause dispersion of iris pigment in mice (TYRP1, GPNMB, LYST, DCT, and MITF). We identified rare mutations, but they were not statistically enriched in PDS patients. Our secondary analyses examined PMEL (previously linked with PDS), MRAP, and 19 other genes. Four MRAP mutations were identified in PDS cases but not in controls (p = 0.016). Immunohistochemical analysis of human donor eyes revealed abundant MRAP protein in the iris, the source of pigment in PDS. However, analysis of MRAP in additional cohorts (415 cases and 1645 controls) did not support an association with PDS. We also did not confirm a link between PMEL and PDS in our cohorts due to lack of reported mutations and similar frequency of the variants in PDS patients as in control subjects. Conclusions We did not detect a statistical enrichment of mutations in melanosome-related genes in human PDS patients and we found conflicting data about the likely pathogenicity of MRAP mutations. PDS may have a complex genetic basis that is not easily unraveled with exome analyses.

Aperture photometry measurements of melanin particles in Krukenberg spindles of the cornea in pigment dispersion syndrome

BACKGROUND: Quantification of melanin pigment release in pigment dispersion syndrome as well as observations of melanin brightness changes can be valuable information in the management of this rare ocular disease. OBJECTIVES: Previous studies have focused on examining the iris pigment epithelium and aqueous humor. Therefore, the aim of this study was to examine the cornea. METHODS: A novel technique was developed for this purpose based on aperture photometry. Slit lamp digital video images of the cornea were recorded. A single frame from each video recording based on the quality was chosen for further processing and analysis. Aperture photometry was performed with AstroImageJ open source software. Aperture selection was performed automatically. Melanin particles displaying a signal-to-noise ratio above 20 were analyzed. RESULTS: A total of 16 melanin particles from the right eye of the patient participating in the study were detected and a further 9 melanin particles from the left eye. The examined area of the cornea measured 348 × 348 pixels in the image. Brightness differed by as much as 8.98 × among particles in the right eye and 2.03 × in the left eye. CONCLUSIONS: It seems feasible for this new method to be potentially used in the monitoring of patients with pigment dispersion syndrome and pigmentary glaucoma as well as in other ocular diseases.

PSEUDOEXFOLIATIVE SYNDROME AS A TRIGGER FOR PSEUDOEXFOLIATIVE GLAUCOMA

Glaucoma is one of the leading causes of blindness and disability worldwide. Pseudoexfoliative glaucoma is known to be the most aggressive and difficult-to-treat form of secondary glaucoma. According to the literature, pseudoexfoliative glaucoma occurs in 25-30% of cases among all open-angle glaucoma. The recent studies have established that a quarter of patients with pseudoexfoliative glaucoma are blind in one eye, and 7% are blind in both eyes. Risk factors for glaucoma include systemic and ophthalmic factors, one of which is the development of pseudoexfoliative syndrome. In patients with pseudoexfoliative syndrome, glaucoma occurs 20 times more often than in the general population of the same age. The purpose of this research is to study the informativeness of individual phenomena of pseudoexfoliative syndrome (PES) in order to improve early diagnosis and prevention of pseudoexfoliative glaucoma. The study included 114 patients diagnosed as having PES. Exclusion criteria were as follows: age up to 45 years, surgery on the eyeball, a history of disease (iridocyclitis, uveitis, corneal pathology, and traumatic eye disease), pigment dispersion syndrome. Along with the standard set of diagnostic measures, patients underwent biomicroscopy in the conditions of maximum drug-induced mydriasis, gonioscopic examination; the proportion of patients was examined by optical coherence tomography (SD-OCT Topson 3D oct-2000FA Plus (version 7/21/003/0)). The study revealed signs of pseudoexfoliative syndrome (deposition of pseudoexfoliative material on various structures of the anterior segment of the eye) in 100% of cases. Higher values of intraocular pressure (from 29 to 34 mm Hg) were found in the patients with elements of blocking the angle of the anterior chamber (narrowing or closing the angle, increased pigmentation and the presence of draining exfoliative conglomerates). The optical coherence tomography study revealed a thinning of the retinal nerve fibres (33.60 ± 0.43 μm), a significant thinning of retinal nerve fibre layer in patients with pseudoexfoliative syndrome and even more significant thinning in 29 patients diagnosed with pseudoexfoliative glaucoma. Thus, we can conclude knowing the microsymptoms of the disease, mandatory investigating the conditions of the maximum drug-induced mydriasis can contribute to detect pseudoexfoliative syndrome even in the initial stages and thus to prevent the development of pseudoexfoliative glaucoma.

Algorithm for Performing Laser Iridectomy in Patients with Angle-Closure Glaucoma and Concomitant Somatic Pathology

Тhe main treatment for angle-closure glaucoma is laser iridectomy. Somatic comorbidity (autoimmune, allergic, chronic infectious diseases) affects the results of laser iridectomy.Purpose: to evaluate in practice the algorithm for applying the method of laser iridectomy in compliance with preventive measures, including medical support before and after surgery, both in patients with concomitant somatic pathology and without it.Patients and methods. The analysis of combined laser iridectomy’s results in 61 patients (94 eyes) was carried out. A method was used to determine the tactics of management the patients with latent stage of angle-closure glaucoma and pigment dispersion syndrome (Patent RU N 2726404), including an assessment of the general immune status based on information about somatic diseases and medications taken. Combined laser iridectomy was performed in two stages in one visit. The first stage is coagulation in the projection of the lacunae at the periphery of the iris; at the second stage, two through holes were formed. All patients received medication in accordance with the algorithm. The level of reactive hypertension was assessed in 1 hour after surgery, on the first and seventh days after the intervention.Results. In case of standard medical support for laser iridectomy, the level of reactive hypertension is higher in the group of patients with concomitant somatic pathology than without it. Adding additions to the standard drug regimen in a group of patients with impaired general immune status ensures that the target intraocular pressure is achieved. The use of an algorithm for performing laser iridectomy in patients with angle-closure glaucoma and concomitant somatic pathology makes it possible to achieve the target intraocular pressure early after surgery and to avoid complications.

A case of dense pigment deposition of the posterior lens capsule

Background Pigment dispersion syndrome (PDS) is a well-known entity which can lead to pigmentary glaucoma (PG). This case report presents a rare presentation of PG with bilateral dense pigment deposits of the posterior lens capsule. Case presentation A 72-year-old male came for his first appointment due to an asymmetric worsening of visual acuity. The examination showed unilaterally severely increased intraocular pressure, bilateral dense pigment deposition of the posterior lens capsule, and a shallow unilateral optic disk excavation. Gonioscopy revealed moderate pigmentation of the angle and a concave configuration of the peripheral iris in both eyes. The standard slit lamp examination showed no transillumination defects of either iris. Optical coherence tomography showed retinal nerve fiber layer (RNFL) thinning in the peripapillary and macular regions. An antiglaucoma medication was prescribed with a good lowering effect. Conclusion Pigment deposition of the posterior lens capsule, which has been rarely reported, is a possible important sign of PDS or PG.