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Purpose Methods Results Conclusion Prospective investigation to determine the prevalence of ocular melanosis in adult Cairn Terriers within the United Kingdom using a previously established staging scheme.Ophthalmic assessment was performed on adult Cairn Terriers, recruited from various geographic locations within the United Kingdom. Examination included gonioscopy, rebound tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy, performed by one examiner (AM).A total of 93 dogs were examined, including 52 females and 41 males, aged between 15 months and 16 years 4 months. Sixty of 93 dogs (64.5%) were >7 years of age. Nine of 93 dogs (9.6%) demonstrated changes consistent with ocular melanosis. Four of 9 (44.4%) had Stage 1 disease and 5 of 9 (55.6%), Stage 2. Stages 3 or 4 were not identified in any dogs. Mean intraocular pressures in affected and unaffected dogs were 14.7 mmHg (range 12–17 mmHg) and 12.8 mmHg (range 5–21 mmHg), respectively. Incomplete pupil dilation was noted in affected dogs following pharmacologic mydriasis.Ocular melanosis was identified in approximately 10% of examined dogs, over half were dogs of breeding age (<7 years of age). It is possible that Grade 1 disease could go undetected, prior to obvious scleral pigment accumulation (Grade 2 disease). It is therefore recommended that dogs undergoing pre‐breeding screens have pre‐dilation assessment of the anterior segment using slit lamp biomicroscopy with subsequent gonioscopy to clearly assess for circumferential thickening of the iris base that might otherwise go undetected. Additionally, regular reassessment of breeding dogs is advised as disease progression could be rapid. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the prevalence and characteristics of pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) in patients diagnosed at a tertiary center eye clinic in Türkiye. Methods: This retrospective, single-center study was conducted at the glaucoma clinic of Haydarpaşa Numune Training and Research Hospital. The files of patients with glaucoma diagnoses between 2015 and 2023 were retrospectively reviewed. The prevalence of PG and PDS, characteristics of the patients, surgical requirements, applied surgical procedures, and risk factors for PG were analyzed. Results: Of the 7,800 files that were reviewed, 50 (0.64%) belonged to patients with PDS or PG. The mean follow-up time was 41.45±34.56 months, and the mean age of the patients was 48.9±12.86 years. Twenty-five (50%) patients were male. Of the 100 eyes reviewed initially, 56 had PDS, 44 had PG, and 17 (30.3%) with PDS progressed to PG during the follow-up period. The mean spherical equivalent (SE) was --1.03±1.62 diopter. In the comparison of eyes with PDS and PG, there were no significant differences with regard to age, sex, SE, central corneal thickness, or best-corrected visual acuity. A median intraocular pressure (IOP) of 17.5 mmHg was achieved on two median glaucoma medications at the last visit. Overall, 10 eyes with PG required surgical and laser interventions for IOP control. Laser peripheral iridotomy (LPI) was performed on nine of these eyes, trabeculectomy with antimetabolite augmentation on two (which had previously undergone LPI), and XEN® gel stent implantation on one. Conclusion: Among the glaucoma patients, the detected frequency of PDS and PG was 0.64%. We did not detect male dominance. The median SE was -1.03±1.62 diopter, indicating mild myopia, which is consistent with the literature. [ABSTRACT FROM AUTHOR]

The phenotypic similarities between exfoliation syndrome (XFS)/exfoliation glaucoma (XFG) and pigment dispersion syndrome (PDS)/pigmentary glaucoma (PG), particularly their association with material deposition in the eye's anterior segment, have prompted investigations into genetic commonalities. This study focuses on the LOXL1 gene, conducting a comprehensive meta-analysis of three candidate gene association studies. We analyzed three single nucleotide polymorphisms (SNPs) of LOXL1: rs1048661, rs3825942, and rs2165241. Our results reveal nominal significance for the exonic SNPs rs1048661 and rs3825942 (p ≤ 0.01), but show no significant association for the intronic SNP rs2165241 (p = 0.83) with PDS/PG. There was homogeneity across study cohorts (I2 = 0), and sensitivity analyses and funnel plots confirmed a lower likelihood of bias in our findings. The lack of a statistically significant association between LOXL1 variants and PDS/PG at p < 0.05 was attributable to the insufficient statistical power of the pooled data, which ranged from 5% to 37% for the three SNPs. This study suggests no association between LOXL1 variants and PDS/PG. Further validation and exploration of XFS/XFG-associated genes in larger and more diverse cohorts would be helpful to determine the genetic correlation or distinctiveness between these conditions. [ABSTRACT FROM AUTHOR]

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion and trabecular meshwork changes, resulting in increased intraocular pressure and potential glaucomatous optic neuropathy. This review summarizes recent progress in PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) and susceptibility loci identified from genome-wide association studies (GSAP and GRM5/TYR). Areas for future research are also identified, especially the development of efficient model systems. While substantial strides have been made in understanding the genetics of PDS/PG, our review identifies key gaps and outlines the future directions necessary for further advancing this important field of ocular genetics. [ABSTRACT FROM AUTHOR]

Background: Ocular melanocytosis was originally described as pigmentary glaucoma and reported in seven dogs of the Cairn Terrier breed. Subsequently, the occurrence of this condition was reported in other breeds of dogs among them a Shih Tzu, recently described. With progression, black pigment spots in the sclera and episclera cover the ciliary cleft. Pigment particles can often be seen suspended in the aqueous and, as they sediment, cover the ventral drainage angle, causing secondary glaucoma. The aim of this study was to describe the clinical and sonographic findings of a Shih Tzu dog with melanocytosis and unilateral secondary glaucoma. Case: A 8-year-old, male, Shih Tzu dog, with a history of progressive darkening of the sclera for 5 years, was referred to the ophthalmological service. The patient underwent routine ophthalmic examination. Slit lamp biomicroscopy revealed anisocoria. In the right eye, diffuse pigmentation of the sclera was observed in almost the entire perilimbal region, and in the iris signs of advanced atrophy with tissue loss between 9 h and 12 h. Nevertheless, zonular ligaments could be observed in this region, as well as a large amount of pigment deposits in the ventral region of the ciliary cleft. Applanation tonometry showed intraocular pressure (IOP) of 14 mmHg. Fundoscopic examination did not reveal abnormal pigmentation, but attenuation of the retinal vessels and in the optic disc was observed. In the left eye, no change was observed to demonstrate the bilaterality of the disease. One month later, the patient returned to the ophthalmology service complaining of an increase in the size of the right eye. Ophthalmic examination revealed moderate buftalmia in the right eye, IOP of 30 mmHg and increased ocular melanosis. Treatment was instituted to control intraocular pressure. Fifteen days after the start of treatment, the IOP decreased to 18 mmHg and it was found that the ophthalmic signs had improved, with a decrease in ocular discomfort. Ultrasound examination showed an increase in the anteroposterior axis and expansion of the anterior chamber, with scattered hyperechogenic spots in the periphery. Ultrasound biomicroscopy (UBM) was performed, in which the presence of obstruction in the ciliary fissure and the presence of punctate echoes between the ciliary fissure and the iris were observed. Four months later, the ophthalmic signs were stable, as well as the IOP (20 mmHg). Currently, the animal is visual in both eyes and with a stable condition in the progression of the disease. Discussion: This condition also known as melanocytosis, pigmentary glaucoma or abnormal pigment deposition, involves the gradual accumulation of pigment-laden cells mainly, melanocytes but also melanophages, in the anterior segment structures including the iris and ciliary body. It is seen in dogs of the Cairn Terriers breed as a hereditary defect, but has been reported in other breeds. Recently the condition was reported in a Shih Tzu, however differently from our work where the condition was unilateral and with a controllable glaucoma. The disorder initially manifests clinically with a progressive bilateral dark peripheral thickening of the iris base, followed by scleral/episcleral plaques of pigment adjacent to the limbus. Signs increase slowly, with pigment clusters in the aqueous and pigmentation in the ventral iridocorneal angle and peripheral endothelium, symptoms are usually bilateral, although not always symmetrical. This is the 1st case of a Shih Tzu with melanocytosis and controlled secondary glaucoma, unilateral, reported in the literature. This is a disease that should be considered as a differential diagnosis of uveal melanomas and melanocytomas. [ABSTRACT FROM AUTHOR]

Introduction: Release of pigments in the anterior chamber is frequently observed in pigment dispersion syndrome, an autosomal dominant disorder marked by bilateral pigment deposition on the anterior and possibly posterior lens capsule, zonules of the lens, trabecular meshwork, and corneal endothelium, in addition to radial, spoke-like transillumination defects in the mid peripheral iris [J Ayub Med Coll Abbottabad. 2017;29(3):412–414 and Optom Vis Sci. 1995;72(10):756–762]. Pigmentation of the anterior lens surface has also been associated with intraocular inflammation, pseudoexfoliation syndrome, siderosis, antipsychotic medication usage, and remnants of the tunica vasculosa lentis [Br J Ophthalmol. 1998;82(11):1344]. Case Presentation: A 23-year-old female presented to our eye clinic with chief complaint of mild blurring of vision in the right eye and inquired about refractive surgery. The patient denied any previous history of ocular inflammation, trauma, surgery, or use of topical or systemic medications. Slit-lamp examination of the right eye anterior segment was within normal limits except for the crystalline lens anterior capsular which showed confluent pigment deposits stellate in shape over the pupillary axis, whereas left eye examination was completely within normal limits. Ophthalmic examination of the posterior segment was normal in both eyes. Based on her previous ophthalmic history and slit-lamp examination of the right eye, a diagnosis of unilateral congenital lenticular pigmentation was made. Conclusion: Congenital lenticular pigmentation is a rare benign entity carrying no surgical indications with a relatively good visual response to optical correction. Recognition of this rare benign condition would add to the ophthalmologist’s differential of ocular pigmentation and avoid unnecessary concern and follow-up in more potentially progressive disorders such as pigmentary glaucoma.

AIM: To observe the medium-long-term efficacy of trabeculectomy in the treatment of pigmentary glaucoma(PG).METHODS: The clinical data of 38 patients(51 eyes)who were diagnosed with PG and received trabeculectomy at the Affiliated Hospital of Yunnan University from January 2010 to September 2022 were retrospectively analyzed. The postoperative follow-up ranged from 3 to 144mo. The intraocular pressure(IOP), visual acuity and refractive status were analyzed, complications were recorded and surgical efficacy was evaluated.RESULTS: The average preoperative use of IOP lowering drugs was 2.90±0.12, with a mean IOP of 18.89±7.40mmHg. The IOP at 3d, 1, 3, 6mo, 1a after surgery and the last follow-up visit were 14.68±5.08, 13.99±2.95, 14.25±2.50, 14.36±2.83, 14.33±2.66, 14.94±1.95mmHg, respectively, and postoperative IOP was significantly lower at all time points than that before surgery(P0.05). During the follow-up period, the visual acuity of all patients was stable, and no endophthalmitis or malignant glaucoma occurred. At the last follow-up, the complete success rate was 90%, the qualified success was 8%, and the failure rate was 2%.CONCLUSION: Trabeculectomy is a safe and effective treatment method for PG, which can effectively control the IOP, and stabilize the visual acuity and relieve the reverse pupil block.

In this case series, we present a methodology for a proof of principle for the development of a unique biomarker for pigmentary glaucoma to detect progression before nerve fiber layer loss. Out of the five patients in this case series, one was excluded because of an outlier due to pseudoexfoliation syndrome with excessively dense pigmentation of the trabecular meshwork. The remaining patients displayed a decreased visual field loss with increased superior to inferior trabecular meshwork ratios. This methodology, though limited due to small sample size, shows that in a limited number of patients, visual field loss is positively correlated with increased superior to inferior trabecular meshwork ratios. The next steps would be to look at patients without glaucoma and patients with pigmentary glaucoma, along with complete inter-eye comparisons for patients with unilateral exfoliation syndrome to act as controls. To our knowledge, this is a novel methodology, and if the pattern holds, it can act as proof of principle for the development of a novel early biomarker for pigmentary glaucoma to improve early intervention and delay vision loss.

Introduction: Release of pigments in the anterior chamber is frequently observed in pigment dispersion syndrome, an autosomal dominant disorder marked by bilateral pigment deposition on the anterior and possibly posterior lens capsule, zonules of the lens, trabecular meshwork, and corneal endothelium, in addition to radial, spoke-like transillumination defects in the mid peripheral iris [J Ayub Med Coll Abbottabad. 2017;29(3):412–414 and Optom Vis Sci. 1995;72(10):756–762]. Pigmentation of the anterior lens surface has also been associated with intraocular inflammation, pseudoexfoliation syndrome, siderosis, antipsychotic medication usage, and remnants of the tunica vasculosa lentis [Br J Ophthalmol. 1998;82(11):1344]. Case Presentation: A 23-year-old female presented to our eye clinic with chief complaint of mild blurring of vision in the right eye and inquired about refractive surgery. The patient denied any previous history of ocular inflammation, trauma, surgery, or use of topical or systemic medications. Slit-lamp examination of the right eye anterior segment was within normal limits except for the crystalline lens anterior capsular which showed confluent pigment deposits stellate in shape over the pupillary axis, whereas left eye examination was completely within normal limits. Ophthalmic examination of the posterior segment was normal in both eyes. Based on her previous ophthalmic history and slit-lamp examination of the right eye, a diagnosis of unilateral congenital lenticular pigmentation was made. Conclusion: Congenital lenticular pigmentation is a rare benign entity carrying no surgical indications with a relatively good visual response to optical correction. Recognition of this rare benign condition would add to the ophthalmologist’s differential of ocular pigmentation and avoid unnecessary concern and follow-up in more potentially progressive disorders such as pigmentary glaucoma. [ABSTRACT FROM AUTHOR]

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Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are two stages within the same ophthalmic disease spectrum, which are known to be affected by race. The prevalence of PDS is underestimated, largely due to its minor clinical symptoms. Although the prevalence of PG is low, the visual impairment associated with PG is extremely severe. The prevalence of PDS-PG is four or more times higher in Caucasians than in Blacks or Asians, and the "classic" PDS in Caucasians has long been used as a benchmark diagnostic criterion. Following extensive research focused on African Americans and Asians, the standard for diagnosing PDS-PG was refined. At the same time, the pathogenesis of PDS is not the same in different races. Hence, the effectiveness of preventive treatment and the need for treatment may not be equivalent in different races. The rate of conversion of PDS to PG is nearly 1/3 in Caucasians and higher in blacks and Asians, requiring more aggressive treatment and monitoring. We systematically searched a PubMed database from inception to March 2022 to provide an overview of research progress in various aspects of PDS-PG. Specifically, this paper considers the effects of race on disease prevalence, clinical manifestation, diagnostic criteria, disease mechanism, hereditary traits, treatment, and prevention to provide an accurate and comprehensive guide for the diagnosis and treatment of PDS-PG in various races. [ABSTRACT FROM AUTHOR]

Amaç: Bu çalışmanın amacı farklı glokom tiplerinde korneanın biyomekanik özelliklerinin incelenmesi ve kornea biyomekaniği ile demografik ve klinik parametreler arasındaki ilişkinin araştırılmasıdır. Gereç ve Yöntem: Bu retrospektif gözlemsel çalışmaya primer açık açılı glokom (PAAG), psödoeksfoliatif glokom (PEG) ve pigmenter glokom (PG) olguları ve kontrol grubu olarak sağlıklı olgular dahil edildi. Tüm olgulara kapsamlı oftalmolojik muayene yapıldı, bilgisayarlı perimetri incelemesi ve optik koherens tomografi (OKT) verileri kaydedildi. Korneal biyomekanik özellikler Corvis ST® (Oculus, Wetzlar, Almanya) ile değerlendirildi. Bulgular: Çalışmaya yaş ortalaması 61,4±11,4 olan 48 glokom olgusu (25 PAAG, 15 PEG, 8 PG; 48 göz) ve 45,2±9,9 olan 51 sağlıklı gönüllü (51 göz) dahil edildi. Birinci aplanasyon hızı (A1V) ve deformasyon amplitüdü (DA) PAAG olgularında diğer gruplara göre daha düşük bulundu. Ayrıca PAAG grubunda 1. aplanasyondaki sertlik parametresi (SP-A1), kontrol grubu ve PEG grubuna kıyasla daha yüksek bulundu. Glokom olgularında, yaş ile stres gerinim indeksi arasında aynı yönlü glokom süresi ile SP-A1 arasında ise ters yönlü bir ilişki bulundu.. Sonuç: Çalışmamızda korneanın PAAG olgularında PEG ve PG olguları ve sağlıklı kornealara kıyasla deformasyona daha dirençli olduğu bulundu. Psödoeksfoliatif glokom ve PG olguları arasında ve bu olgular ile kontrol grubu arasında kornea biyomekaniği açısından bir fark saptanmadı..

We present a patient with concurrent pigmentary glaucoma, bilateral central serous chorioretinopathy and unilateral optic disc pit, and propose a possible association of these conditions. Comprehensive ophthalmic examination of a 36-year-old man who was complaining of blurry vision and pain in the eyes showed reduced visual acuity on the left eye, elevated intraocular pressure in the right eye, bilateral signs of pigment dispersion syndrome, and bilateral central serous chorioretinopathy, combined with optic disc pit in the left eye. Visual field and optical coherence tomography findings demonstrated functional and structural glaucoma changes. Choroidal circulation abnormalities were observed by angiographic methods. Genetic and developmental anomalies of the external layer of the optic disc cup that gives rise to many anterior and posterior eye segment structures suggest a possible association of a clinical condition characterized by the combination of pigmentary glaucoma, central serous chorioretinopathy and optic disc pit. Future research would enable to determine proper diagnostic protocols, treatment and follow-up procedures for this chronic-progressive disorder.

Purpose: To compare the intraocular pressure (IOP) profile and the incidence of IOP spikes following selective laser trabeculoplasty (SLT) between pigmentary glaucoma (PG) and primary open-angle glaucoma (POAG)., Materials and Methods: Retrospective comparative study of 65 PG eyes of 51 patients matched with 65 POAG eyes of 65 patients who received SLT. Matching was done based on age, gender, glaucoma severity, pre-laser IOP, and number of medications. Post-SLT IOP spike was defined as IOP elevation ≥5mmHg, 30-45 min after the laser., Results: In PG and POAG groups, the average age was 62.33 ± 9.18 and 62.58 ± 9.19 years (p = 0.95). The glaucoma severity (p = 0.708), baseline IOP (PG = 21.61 ± 1.34mmHg vs. POAG = 21.13 ± 5.09mmHg, p = 0.943), and number of topical glaucoma medications(PG = 2.34 ± 1.34 vs. POAG = 2.1 ± 1.41, p = 0.342) were comparable. More PG patients were on oral acetazolamide (PG = 26.15% vs. POAG = 1.5%, p < 0.001). Average logMAR visual acuity was significantly higher in the POAG group (0.207 ± 0.3 vs. 0.192 ± 0.37, p = 0.012). Eyes with PG received lower laser energy (POAG = 63.65 ± 22.03 mJ vs. PG = 43.71 ± 25.68 mJ, p < 0.001). IOP spikes were recorded in 5 PG eyes (7.6%) and none in the POAG group (p = 0.058). Failure rates were similar (PG = 50.7% and POAG = 43.1%, p = 0.205). In multivariable analysis, only pre-laser IOP (coefficient = 2.154 [CI: 0.765-3.543], p = 0.003) was a significant predictor of IOP change percentage after 12 months., Conclusions: SLT was comparably effective in both PG and POAG. IOP spikes were observed only in the PG group, though the total laser energy was lower in this group compared with POAG., Competing Interests: Declaration of conflicting interestsThe author(s) declare they have no relevant financial disclosure. The following is the full list of disclosures for each author: NNK (Kolomeyer) received research support from AbbVie/Allergan, Guardion Health Services Inc, Equinox, Nicox, Olleyes, Santen, Glaukos, Diopsys, and Aerie, and consulting fees from AbbVie/Allergan (myself, spouse), Regeneron (spouse), Alimera (spouse), Genentech (spouse); AGS (Shukla) has received research support from AbbVie, Inc, and consulting fees from AbbVie, Inc., and also participates on a Data Safety Monitoring Board or Advisory Board for AbbVie, Inc; RR (Reza) received research support from Olleyes, Equinox, and Allergan; DL (Lee) has received research support from Allergan, Equinox, Glaukos, Mati, Nicox, Olleyes, and Santan, lecture fees from Glaukos, and consulting fees from Quidel Eye Health; JSM (Myers): Research grants: AbbVie, Elios, Equinox, Glaukos, Guardian, Laboratories Thea, Nicox, Olleyes, Santen; Consulting: AbbVie, Avisi, Embark Neuro, Glaukos, Olleyes; MRM (Moster): Abbvie: Consultant/Advisor, LectureFees/SpeakersBureau, GrantSupport, ArcScan: Advisory Board Aerie Pharmaceuticals: Consultant/Advisor, LectureFees/Speakers Bureau, Grant Support, Alcon Laboratories Inc.: Consultant/Advisor, Lecture Fees/Speakers Bureau, Grant Support, Allergan: Consultant/Advisor, LectureFees/SpeakersBureau, Grant Support Bausch + Lomb: Lecture Fees/Speakers Bureau, Grant Support, Glaukos: Grant Support, Inn Focus: Grant Support, MedEdicus: LectureFees/SpeakersBureau, New World Medical, Inc.: Grant Support, Novartis, Alcon Pharmaceuticals: Lecture Fees/Speakers Bureau, Regeneron: Advisor, Santen, Inc.: Consultant/Advisor, Grant Support, Thea Inc.: Grant Support, Advisor. W. L. Gore & Associates, Inc.: Advisor ; SH, SS, NM, AM, ED, CS, and MJP declare they have no financial disclosures.

The molecular mechanisms underlying the pathogenesis of pigment dispersion syndrome and pigmentary glaucoma remain unclear. In pedigree-based studies, familial aggregation and recurrences in relatives suggest a strong genetic basis for pigmentary glaucoma. In this study, we aimed to identify the genetic background of two Chinese pedigrees with pigmentary glaucoma. All members of these two pedigrees who enrolled in the study underwent a comprehensive ophthalmologic examination, and genomic DNA was extracted from peripheral venous blood samples. Whole-exome sequencing and candidate gene verifications were performed to identify the disease-causing variants; in addition, screening of the CPAMD8 gene was performed on 38 patients of sporadic pigmentary glaucoma. Changes in the structure and function of abnormal proteins caused by gene variants were analyzed with a bioinformatics assessment. Pigmentary glaucoma was identified in a total of five patients from the two pedigrees, as were compound heterozygous variants of the CPAMD8 gene. No signs of pigmentary glaucoma were found in carriers of monoallelic CPAMD8 variant/variants. All four variants were inherited in an autosomal recessive mode. In addition to the 38 patients of sporadic pigmentary glaucoma, 13 variants of the CPAMD8 gene were identified in 11 patients. This study reported a possible association between CPAMD8 variants and pigment dispersion syndrome/pigmentary glaucoma. [ABSTRACT FROM AUTHOR]

The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses. [ABSTRACT FROM AUTHOR]

To identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients and to further understand the genetic and potentially causal relationships between PDS and associated risk factors. A 2-stage genome-wide association meta-analysis with replication and subsequent in silico analyses including Mendelian randomization. A total of 574 cases with PG or PDS and 52 627 controls of European descent. Genome-wide association analyses were performed in 4 cohorts and meta-analyzed in 3 stages: (1) a discovery meta-analysis was performed in 3 cohorts, (2) replication was performed in the fourth cohort, and (3) all 4 cohorts were meta-analyzed to increase statistical power. Two-sample Mendelian randomization was used to determine whether refractive error and intraocular pressure exert causal effects over PDS. The association of genetic variants with PDS and whether myopia exerts causal effects over PDS. Significant association was present at 2 novel loci for PDS/PG. These loci and follow-up analyses implicate the genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) and glutamate metabotropic receptor 5 (GRM5) /TYR (lead SNP: rs661177, P = 3.9×10-9) as important factors in disease risk. Mendelian randomization showed significant evidence that negative refractive error (myopia) exerts a direct causal effect over PDS (P = 8.86×10-7). Common SNPs relating to the GSAP and GRM5/TYR genes are associated risk factors for the development of PDS and PG. Although myopia is a known risk factor, this study uses genetic data to demonstrate that myopia is, in part, a cause of PDS and PG. [ABSTRACT FROM AUTHOR]

Abstract 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.

To compare the quantitative measurements of the anterior chamber angle (ACA) and iris parameters in patients with juvenile open-angle glaucoma (JOAG), pigmentary glaucoma (PG), and healthy controls using anterior segment optical coherence tomography (AS-OCT).Methods: This was a retrospective, cross-sectional study of 25 eyes with JOAG, 25 eyes with PG, and 25 control eyes. Anterior chamber depth, angle-opening distance 500 and 750, trabecular-iris space 500 and 750, scleral spur angle, iris thickness (IT, measured at the thickest part), and iris bowing were obtained using AS-OCT (Visante" OCT 3.0 Model 1000, Carl Zeiss Meditec, Inc).Results: The quantitative ACA parameters were found to be significantly higher in JOAG and PG patients compared to healthy controls (P < 0.001); there was no significant difference between the eyes with JOAG and PG (P > 0.05). In eyes with JOAG and PG, there was significantly backward bowing of the iris in temporal and nasal angles compared to control subjects (P < 0.001). Median iris bowing was not significantly different between the patients with JOAG and PG (P > 0.05). The temporal and nasal angle iris thickness were significantly thinner in eyes with JOAG than the eyes with PG (P < 0.001) and age-matched control subjects (P < 0.001). The median IT did not differ between the patients with PG and control subjects (P > 0.05). In patients with JOAG, the intraocular pressure (IOP) was inversely correlated with IT (r = -0.43, P < 0.05).Conclusion: AS-OCT provided quantitative data on the ACA and iris parameters in JOAG and PG. The evaluation of the ACA and iris structures using AS-OCT revealed higher ACA measurements and posterior bowing of the iris in patients with JOAG and PG. Furthermore, the patients with JOAG were found to have thinner IT than the ones with PG and healthy controls. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the biomechanical properties of the cornea in different types of glaucoma and the relationship between corneal biomechanics and demographic and clinical parameters. Materials and Methods: Primary open-angle glaucoma (POAG), pseudoexfoliative glaucoma (PEG) and pigmentary glaucoma (PG) cases and healthy subjects as a control group were included in this retrospective observational study. Detailed ophthalmological examination was performed, computerized perimetry and optical coherence tomography (OCT) data were recorded in all cases. Corneal biomechanical properties were evaluated with Corvis ST® (Oculus, Wetzlar, Germany). Results: Forty-eight glaucoma cases (25 POAG, 15 PEG, 8 PG; 48 eyes) with a mean age of 61.4±11.4 years and 51 healthy volunteers (51 eyes) with a mean age of 45.2±9.9 years were included in the study. First applanation velocity (A1V) and deformation amplitude (DA) were lower in POAG cases than in other groups. In addition, the stiffness parameter (SP-A1) in the 1st applanation was higher in the POAG group compared to the control and PEG groups.. In glaucoma cases, a positive correlation was found between age and stress strain index, and an inverse relationship between glaucoma duration and SP-A1 Conclusion: The cornea was more resistant to deformation in POAG cases compared to PEG and PG cases and healthy corneas. There was no difference in corneal biomechanics between PEG and PG cases, and between these cases and the control group.. [ABSTRACT FROM AUTHOR]

Abstract 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.

Pigment dispersion syndrome and pigmentary glaucoma are two conditions characterized by pigment dispersion originating from the posterior part of the iris and its accumulation on the trabecular meshwork, corneal endothelium, and anterior surface of the lens. The pigment on the trabecular meshwork can cause chronic inflammation with a secondary reduction of its function and an increase in intraocular pressure. The case presented represents a typical example of pigmentary glaucoma in a myopic patient in which all the signs, symptoms, and complications typical of these pathologies were present. We report and describe an 8-year-long follow-up period with clinical and instrumental examinations.

Purpose: To investigate safety and efficacy of the XEN gel stent in patients with pigmentary glaucoma (PG)., Methods: A retrospective analysis of 26 eyes of 19 patients with PG undergoing XEN gel stent implantation was performed. Best-corrected visual acuity, intraocular pressure (IOP), and number of antiglaucoma medications were analyzed preoperatively, and at 2 weeks and 3, 6, 12, and 24 months after surgery. Success, needling, and complications were analyzed. Complete success was defined as an IOP reduction of >20% and achieving a target IOP of ≤18, ≤15, or ≤12 mmHg without antiglaucoma medication. Qualified success was indicated if the IOP target was reached with or without medication., Results: Mean IOP decreased significantly from 27.6 ± 14.3 (standard deviation, SD) mmHg to 14.3 ± 4.6 mmHg after one year ( p  < 0.001) and 15.1 ± 2.7 mmHg ( p  < 0.001) after two years. The median number of hypotensive drugs declined significantly from 4 (range: 3-5) to 0 (0-2) and 0 (0-3) after one and two years, respectively. After two years, complete success with an IOP of ≤18 mmHg and ≤15 mmHg was achieved in 73.1% and 61.5%, respectively. Half of the eyes required needling after a median time of 8 months (0.5-34 months). No sight-threatening complications were observed., Conclusion: The XEN gel stent is a safe and effective surgical treatment option for PG. Needling is an important part of the procedure and should be communicated preoperatively to the patients., Competing Interests: Declaration of conflicting interestsBV has received speaker honoraria from AbbVie, Santen and Novartis. CJG, EN, and DAW declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose/Aim: Glaucomatous optic neuropathy (GON) remains the world's leading cause of irreversible blindness. Treatments including topical medications are directed at reducing intraocular pressure (IOP), the most significant risk factor for GON. Current medications, while generally effective, are limited by insufficient response and side-effects in some patients. In search of a more targeted therapy that acts downstream of existing medications that has a potential for a lower side effect profile, our laboratory has identified Stanniocalcin-1 (STC-1), a multifunctional hormone, as an effector molecule in latanoprost-mediated IOP reduction with similar IOP-lowering efficacy as latanoprost in normotensive mice. Materials and methods: To investigate whether STC-1 can also reduce IOP in ocular hypertensive mice, we used a steroid-induced ocular hypertensive mouse model characterized by trabecular meshwork dysfunction as well as the DBA/2J mouse as an inherited model of pigment dispersion and secondary angle closure. Steroid-induced ocular hypertension was induced by weekly injections of dexamethasone into the conjunctival fornix of wild-type C57BL/6J mice (6–8 months old). After confirmation of the steroid response, mice were administered STC-1 or phosphate buffered saline (PBS) topically once daily for six weeks. For DBA/2J mice (14 months old), after baseline IOP measurements, mice were treated topically once daily with STC-1 or PBS for 5 days and IOP was assessed twice daily. Results: In steroid-induced ocular hypertensive mice, STC-1 lowered IOP by 26% (P <.001, week three) and maintained this level of IOP reduction throughout the remainder of the treatment period (P <.001, week six). In DBA/2J mice, STC-1 lowered IOP by 37% (P <.001). Conclusions: Together, these data show that STC-1 reduced IOP in two models of ocular hypertension with different mechanisms of outflow obstruction. [ABSTRACT FROM AUTHOR]

Purpose: To compare the corneal densitometry (CD) measurements in patients with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG). Materials and Methods: This prospective comparative study included 22 eyes with PG, 19 eyes with PDS and 21 control individuals. After complete ophthalmological examination, all the eyes had central corneal thickness (CCT) and CD measurements by densitometry software of Pentacam HR-Scheimpflug corneal topography over a 12-mm diameter of the cornea. Chi-Square, Kolmogorov-Smirnov, analysis of variance, and Tukey's post-hoc tests were used for statistical analysis. Results: All the eyes with PG were under prostaglandin monotherapy. The mean CCT was significantly higher in PG cases than the other groups (p=0.01). The mean CD of anterior layer at the 0-2 mm was significantly higher in PG than PDS cases and normal subjects (p=0.007). The mean CD of total layer at the 0-2 mm was significantly higher in PG cases than control subjects (p=0.03). The mean CD of anterior layer at the 2-6 mm was significantly higher in PG than PDS cases (p=0.04). There were no significant differences of CD in other zones and layers between the groups. Conclusion: The presence of Krukenberg spindle, higher age in PG and the probable effects of glaucoma might cause corneal backscatter of light and increased CD particularly in anterior layers in central zones of cornea. [ABSTRACT FROM AUTHOR]

Pigment dispersion syndrome (PDS) represents a clinical spectrum of a relatively common and usually underdiagnosed phenomenon produced by spontaneous pigment dispersion from the iris into the anterior segment. PDS is often bilateral, has no gender predisposition, and presents at a young age, particularly in myopes. Although most patients experiencing an episode of pigment dispersion are asymptomatic, extreme photophobia, ocular pain, redness, and blurred vision may occur. Other characteristic signs are iridolenticular contact, concave iris configuration, 360° peripheral iris transillumination, and pigment deposition on the anterior chamber angle or the corneal endothelium (Krukenberg spindle). Early PDS diagnosis is crucial to detect patients with pigment-related ocular hypertension (POHT) that can eventually lead to pigmentary glaucoma (PG). The latter represents a sight-threatening condition in which mechanical, environmental, and genetic factors contribute to optic nerve damage. In this review, we update the pathogenic mechanisms involved in the clinical spectrum of the disease. We describe its clinical presentation, ophthalmologic manifestations, and complications, including the factors influencing the development of POHT and PG. Because PDS has variable clinical presentations that lead to misdiagnoses, we emphasize the differential diagnosis and the actual therapeutic strategies according to disease status. [ABSTRACT FROM AUTHOR]

BackgroundThe molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP.ResultsWe tested the role of NK cells in disease etiology by genetically modifying the B6.D2-Gpnmb(R150X) Tyrp1(b) strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of Gpnmb(R150X) Tyrp1(b) mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage.ConclusionOur previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression.

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. [ABSTRACT FROM AUTHOR]

Purpose of the study was to investigate the effectiveness of selective laser trabeculoplasty (SLT) in various forms of glaucoma, in the initial, advanced and far-advanced stages of the disease.Material and methods. An analysis of the effectiveness of the treatment of 132 eyes (132 patients), who were examined and treated in the department of glaucoma diagnostics and treatment of Ekaterinburg Center of Eye Microsurgery Federal State Institution, has been performed from 2016 to 2018. The study included a group of patients with primary open-angle, pseudoexfoliation, pigment, and combined forms of glaucoma previously not operated. Laser iridotomy was previously performed in patients with pigmented and combined glaucoma. The efficacy of SLT was assessed by the level of intraocular pressure (IOP) before SLT, after three days, 1, 6 and 12 months, using the perimetric MD index and according to the need for repeated surgical interventions during the observation period. Results. By the end of the observation period after SLT in patients with initial glaucoma IOP decreased by 5.1 mm Hg (by 20.7 %), with advanced glaucoma – by 6.3 mm Hg (by 25.7 %), with far-advanced glaucoma – by 6.8 mm Hg (by 31 %) compared to baseline values. Analysis of SLT effectiveness depending on the form of the disease showed that 12 months after surgery IOP in patients with primary open-angle glaucoma decreased by 5.5 ± 1.32 mm Hg (23 %) compared with baseline figures, and in patients with combined glaucoma – by 5.5 ± 1, 5 mm Hg (22.8 %). In the follow-up period from 6 to 12 months after SLT, 88 % of patients with pseudoexfoliation glaucoma, 64 % of patients with pigmentary glaucoma and 34 % of patients with combined glaucoma underwent non-penetrating deep sclerectomy, 15 % of patients with primary open-angle glaucoma underwent repeated SLT.Conclusion. SLT is the safe and effective method of glaucoma treating. In all forms and stages of glaucoma, target IOP was obtained, as evidenced by stabilization of retinal sensitivity by automated perimetry, but the hypotensive effect after SLT in patients with pseudoexfoliation glaucoma and pigmentary glaucoma lasted less than 1 year.

Pigment dispersion syndrome (PDS) is a clinical entity that is characterized with anomalous irido-zonular contact leading pigment dispersion throughout the anterior segment. Clinical presentation includes pigmented cells on the corneal endothelium, an increased pigmentation of the trabecular meshwork, and mid-periphery transillumination defects of iris. The syndrome is usually bilateral and more common in myopic individuals and young male adults. Also it can be associated with ocular hypertension or glaucoma. Pigmentary glaucoma (PG) is a kind of secondary open-angle glaucoma and is caused by occlusion of trabecular meshwork by pigmentary cells and reduction in the aqueous humor efflux. In this review, we will discuss clinical characteristics, pathogenesis and current management of PDS and PG. [ABSTRACT FROM AUTHOR]

Introduction: Pigmentary Glaucoma (PG) and Pigment Dispersion Syndrome (PDS) are two different spectrums of a single disease. Since the disease is seen in younger population and is rapidly progressive blinding disease, therefore early diagnosis and treatment will reduce the burden of the disease and improve the quality of life. Aim: The aim of this study was to evaluate clinical characteristics of PDS and PG patients in eastern part of Uttar Pradesh. Materials and Methods: This was a two years (1st January 2018 to 31st December 2019) hospital-based retrospective cross-sectional study of patients who attended the glaucoma clinic. Diagnosis of PDS was made when they had normal optic disc, normal visual field {with or without increased Intra Ocular Pressure (IOP)} and at least two of the following three signs were found clinically: Krukenberg spindle, homogenous moderate-to-heavy (≥Spaeth 2+) Trabecular Meshwork (TM) pigmentation, and any degree of zonular and/or lenticular pigment granule dusting. Patients with PDS were diagnosed with PG, if they had two or more of the following findings: initial IOP >21 mmHg, glaucomatous optic nerve damage or glaucomatous visual field loss. Various parameters such as influence of demographics, IOP, Best-Corrected Visual Acuity (BCVA), Central Corneal Thickness (CCT), Mean Deviation (MD), Visual Field Index (VFI %), spherical equivalent and clinical finding of anterior segment of study patients were analysed. Mean, standard deviation and percentage were calculated using GraphPad Instat version 3.0. Results: Among 40 patients, nine eyes of the six patients had myopia of -0.5D or greater, with mean refractive error of -3.55±4.72 spherical equivalent. The average baseline IOP in study patients (PDS+PG), was 30.21±11.42 mmHg. Twenty four (60%) patients, either in one or both eyes had glaucoma, secondary to PDS at the initial diagnosis. Thirty three (82.5%) patients had Krukenberg spindles. Homogeneous TM pigmentation was seen in all patients. Typical spoke-like radial Iris Transillumination Defects (ITDs) were not observed in any of the patients except in one patient, who had isolated short slitlike trans-illumination defects in iris crypts. Conclusion: It can be concluded that PDS patients with normal optic disc and visual field and raised IOP, should be started prophylactic treatment and needs to be monitored more closely. Thus, the finding of PDS in Indians should alert the ophthalmologist to look for glaucoma during the initial examination. [ABSTRACT FROM AUTHOR]

Pigment dispersion syndrome and pigmentary glaucoma are two conditions characterized by pigment dispersion originating from the posterior part of the iris and its accumulation on the trabecular meshwork, corneal endothelium, and anterior surface of the lens. The pigment on the trabecular meshwork can cause chronic inflammation with a secondary reduction of its function and an increase in intraocular pressure. The case presented represents a typical example of pigmentary glaucoma in a myopic patient in which all the signs, symptoms, and complications typical of these pathologies were present. We report and describe an 8-year-long follow-up period with clinical and instrumental examinations. [ABSTRACT FROM AUTHOR]

Importance: Use of the trabecular micro‐bypass stent with cataract surgery is well established to be safe and effective in primary open‐angle glaucoma. This is the first study to exclusively evaluate use of the device in pigmentary glaucoma. Background: This study aimed to investigate the safety and efficacy of a trabecular micro‐bypass stent in combination with cataract surgery in pigmentary glaucoma. Design: Retrospective, consecutive case series. Participants: Twenty‐four eyes of 12 patients with pigmentary glaucoma implanted with one trabecular micro‐bypass stent with concomitant cataract surgery. Methods: Baseline data was collected and compared to the following postoperative time points: 1 day, 1 week, 1 month out to 36 months (M36) after the procedure. Main Outcome Measures: These included intraocular pressure (IOP), number of glaucoma medications and need for additional surgery. Results: At M36 there was a 25% reduction in IOP to 14.68 ± 3.0 (P <.01) from 19.50 ± 6.7 mmHg at baseline. The mean number of glaucoma medications was 0.75 ± 1.0 prior to the surgery and 0.59 ± 0.6 (P >.05) at 36 M. At the 36 M time‐point, 95% of eyes had IOP ≤ 18 mmHg and 68% of eyes were ≤ 15 mmHg. No eyes underwent a secondary glaucoma procedure. Conclusions and Relevance: The insertion of a single trabecular micro‐bypass stent in combination with cataract surgery effectively provides a sustained reduction in IOP up to 3 years after surgery in patients with pigmentary glaucoma. The safety profile is favourable with low rate of IOP spikes and no patients requiring additional surgery. [ABSTRACT FROM AUTHOR]

Glaucoma, one of the leading causes of irreversible blindness worldwide, is a complex and heterogenous disease. While environmental factors are important, it is well-recognized that the disease has a strong heritable component. With the advent of large-cohort genome wide association studies, a myriad of genetic risk loci has been linked to different forms of glaucoma. Animal models have been an indispensable tool in characterizing these loci, especially if they lie within coding regions in the genome. Not only do these models connect genotype to phenotype, advancing our understanding of glaucoma pathogenesis in the process, they also have valuable utility as a platform for the pre-clinical testing of potential therapies. In this review, we will outline genetic models used for studying the major forms of glaucoma, including primary open angle glaucoma, normal tension glaucoma, primary angle closure glaucoma, pigmentary glaucoma, pseudoexfoliation glaucoma, and early onset glaucoma, including congenital and developmental glaucoma, and how studying these models have helped shed light on human glaucoma. [ABSTRACT FROM AUTHOR]

In this case series, we present a methodology for a proof of principle for the development of a unique biomarker for pigmentary glaucoma to detect progression before nerve fiber layer loss. Out of the five patients in this case series, one was excluded because of an outlier due to pseudoexfoliation syndrome with excessively dense pigmentation of the trabecular meshwork. The remaining patients displayed a decreased visual field loss with increased superior to inferior trabecular meshwork ratios. This methodology, though limited due to small sample size, shows that in a limited number of patients, visual field loss is positively correlated with increased superior to inferior trabecular meshwork ratios. The next steps would be to look at patients without glaucoma and patients with pigmentary glaucoma, along with complete inter-eye comparisons for patients with unilateral exfoliation syndrome to act as controls. To our knowledge, this is a novel methodology, and if the pattern holds, it can act as proof of principle for the development of a novel early biomarker for pigmentary glaucoma to improve early intervention and delay vision loss., Competing Interests: DL is a consultant for Sight Sciences, Alcon, Nidek. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Laroche, Brown, Sinon, Martin, Ng and Sakkari.)

Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease-specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re-think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous-blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology., (© 2023 The Authors. WIREs Mechanisms of Disease published by Wiley Periodicals LLC.)

Introduction: Pigment dispersion syndrome (PDS) is a condition where anomalous iridozonular contact leads to pigment dispersion throughout the anterior segment and the released pigment is abnormally deposited on various ocular structures. Clinical presentation: The clinical presentation of PDS is defined by the presence of pigmented cells on the corneal endothelium, an increase of pigmentation of the trabecular meshwork, and mid-periphery transillumination defects of the iris. This syndrome, more common in myopes, is usually bilateral and can be associated with ocular hypertension or glaucoma. Secondary open-angle pigmentary glaucoma (PG) can develop due to reduction of the outflow of aqueous humour and consequent increase in intraocular pressure leading to glaucomatous optic neuropathy. Diagnosis of PG is commonly between 40 and 50 years of age, occurring more frequently in men. The advent of ultrasound biomicroscopy and anterior segment optical coherence tomography has contributed to enhancing our knowledge on the condition. Typical alterations of the anterior segment are the posterior insertion of the iris and iris concavity. Treatment of PG should be initiated early to hinder disease progression, glaucomatous damage, and vision loss. Management is based on medical therapy, laser iridotomy, selective laser trabeculoplasty, and filtration procedures. Conclusions: The differential diagnosis of PDS with other disorders can be challenging and awareness of the condition together with meticulous ophthalmologic examination allows early diagnosis followed by appropriate management strategies. The present review is a comprehensive report on the clinical characteristics, pathogenesis, current management, and status quo of PDS and PG. [ABSTRACT FROM AUTHOR]

Purpose: Dysfunction of the trabecular meshwork (TM) in pigmentary glaucoma contributes to increased aqueous humor outflow resistance and intraocular pressure. In this study, we investigated the effect of pigment dispersion on trabecular meshwork cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then, analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose migrate, and contraction was quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: Stress fiber formation was increased in the pigment dispersion group (P) (60.1 ± 0.3%, n = 10) compared to control (C) (38.4 ± 2.5%, n = 11, p < 0.001). Phagocytosis declined (number of cells with microspheres in P = 37.0 ± 1.1% and in C = 68.7 ± 1.3%, n = 3, p < 0.001) and migration was reduced after 6 h (cells within the visual field over 6 h in P = 28.0.1 ± 2.3 (n = 12) and in C = 40.6 ± 3.3 (n = 13), p < 0.01). Pigment induced contraction at 24 h onwards (p < 0.01). Microarray analysis revealed that Rho signaling was central to these responses. Conclusion: Exposure of TM cells to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model.Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/ml for 48 h before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated.Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 h. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 h (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed.Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load. [ABSTRACT FROM AUTHOR]

Background: Though trabeculectomy is often performed on patients with medically refractive pigmentary glaucoma (PG), the clinical outcomes of surgical treatment on PG remain unknown. The aim of this study was to summarize the long-term efficacy and safety of trabeculectomy on PG. Methods: This was a prospective case series observational study. Eighteen consecutive PG patients were followed up for 8 years after trabeculectomy from May 2006 to April 2007. Visual acuity (VA), best-corrected visual acuity (BCVA), slit lamp biomicroscopy, intraocular pressure (IOP) measurement, Humphrey visual field analysis (VFA), and stereoscopic funduscopy were performed on admission and every 6 months after the surgery. Postoperative IOP, VA, BCVA, VFA, adjunctive anti-glaucoma medication, treatment-related side-effects, changes in blebs, and main clinical findings in the anterior segment of PG were recorded and compared with the baseline. Results: Eighteen PG eyes from 18 patients, with average preoperative IOP of 34.5 ± 4.7 mmHg (range: 21–47 mmHg, 1 mmHg=0.133 kPa) were enrolled in this study. All enrolled patients completed the follow-up visits and required examinations. Eight years after trabeculectomy, all surgical eyes (18/18) had satisfactory IOP control with an average of 13.7 ± 2.5 mmHg (range: 9–19 mmHg), which was significantly lower than baseline (P = 0.001). Majority (15/18) of the PG eyes had stable VA, BCVA, VFA, and optic disc cupping parameters. Functional blebs still existed in 12/18 of the PG eyes at the last follow-up visit. Unanimously, pigmentation in the anterior segment attenuated with time after surgical treatment. No severe side-effects were recorded in any of the surgical eyes. Conclusions: All surgical PG eyes in this study had satisfactory IOP control 8 years after the surgery with well-preserved visual function. The long-term efficacy and safety of trabeculectomy are promising in PG patients.

Purpose: The purpose of this study is to compare the peripapillary vascular density in patients with various types of open-angle glaucoma (primary open-angle glaucoma, pseudoexfoliative glaucoma and pigmentary glaucoma) with healthy subjects by optic coherence tomography angiography (OCTA)., Methods: Twenty-seven eyes with diagnosed POAG, thirty-four eyes with diagnosed PXG, twenty eyes with diagnosed PG and thirty eyes of healthy individuals were included in our study. Peripapillary vessel density measurements were performed with all images; (AI-DD), intra-disc (ID-DD) and peripapillary (PP-DD); measurement of vascular density in the radial peripapillary capillary network was performed by OCTA. The Kruskal-Wallis test and post-hoc test were performed for statistical analysis., Results: AI-DD was 50.76±2.07% in the healthy group, 47.12±2.57% in POAG, 39.71±6.64% in PXG, and 43.37±1.55% in PG. ID-DD was 50.49±3.74% in the healthy group, 49.51±6.83% in POAG, 38.42±13.46% in PXG, and 40.9±4.45% in PG. PP-DD was 51.26±3.12% in the healthy group, 50.13±3.04% in POAG, 42.31±7.31% in PXG, and 47.6±1.40% in PG. While it was found that all image and intra-disc vascular density measurements were statistically significantly lower in the PG and PXG group compared to the healthy group and the POAG (P<0.001), there was no significant difference between PXG and PG or between the control group and POAG., Conclusions: The lower radial peripapillary capillary density in PXG and PG compared to the POAG and healthy groups suggests that the blood flow around the optic disc is negatively affected in these patients., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)