Intrascleral intraocular lens fixation with ab interno trabeculotomy in patients with exfoliation glaucoma with lens subluxation.

PURPOSE: To evaluate the surgical outcomes of intrascleral intraocular lens (IOL) fixation using ab interno trabeculotomy (LOT) in patients with exfoliation glaucoma with lens subluxation. STUDY DESIGN: Retrospective case series. METHODS: Twenty eyes of 18 patients with exfoliation glaucoma and lens or IOL subluxations were included. Three success criteria were based on postoperative intraocular pressure (IOP) (A, ≤15 mmHg; B, ≤18 mmHg; C, ≤21 mmHg). The IOP, number of glaucoma medications, and visual acuity were compared before and after surgery. Success probability was analyzed using Kaplan-Meier survival curves. Cox proportional hazards' regression models were used to examine prognostic factors for surgical failure. RESULTS: The mean follow-up period was 23.4 ± 7.8 months. The mean IOP significantly decreased from 23.2 ± 6.8 mmHg preoperatively to 14.0 ± 4.4 mmHg at 1 year postoperative (P<0.001). Postoperative hyphema and vitreous hemorrhage were observed in seven and 15 eyes, respectively, and washout in the anterior chamber or vitreous cavity was performed in four eyes. Postoperative IOP spikes and hypotony were observed in four eyes each. Glaucoma reoperation was performed in two eyes. The success rates at 12 months were 65%, 85%, and 90% using criteria A, B, and C, respectively. The IOP at 1 month after surgery was a significant prognostic factor for surgical failure according to criterion A (hazard ratio: 1.08; P=0.034). CONCLUSION: Intrascleral IOL fixation combined with microhook LOT is a promising option in cases of exfoliation glaucoma with subluxated lens/IOL; however, the high rate of postoperative hyphema and vitreous hemorrhage should be noted.

Is pseudoexfoliation glaucoma a neurodegenerative disorder?

Pseudoexfoliation (PEX) is a systemic age-related progressive disorder with ocular manifestations. The earlier stage of the disease, pseudoexfoliation syndrome (PEXS) involves deposition of white fibrillar aggregates on anterior and posterior eye tissues. It is also the cause of most common form of secondary glaucoma known as pseudoexfoliation glaucoma (PEXG). Studies in the past decade highlight the role of many genetic and environmental factors as the underlying cause of PEX pathogenesis. Latest research findings by various researchers and us present the view of PEX as a type of neurodegenerative disorder. Epidemiological studies have shown association of PEX with different forms of neurodegenerative diseases like Alzheimer's, agerelated macular degeneration and open angle glaucoma. Also, sharing of common genetic risk factors, abnormal protein aggregation and most importantly, progressive degeneration of neurons with age are some of the identifiable features seen in both PEX and other neurodegenerative diseases. In this review, we have compared the pathological symptoms and factors involved in the disease manifestation of PEXG with various forms of neurodegenerative disorders and categorized PEXG as a progressive neurodegenerative disorder.

Intraocular lens power calculations in eyes with pseudoexfoliation syndrome.

To compare refractive outcomes after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes and to investigate the accuracy of 3 intraocular lens (IOL) calculation formulas in these eyes. In this prospective comparative study 42 eyes (PEX group) and 38 eyes (control group) of 80 patients were included. The follow-up was 3 months. The refractive prediction error (RPE), mean absolute error (MAE), median absolute error (MedAE) and the percentages of eyes within ± 0.25 D, ± 0.5 D, ± 1.0 D and ± 2.0 D of prediction error were calculated. Three IOL calculation formulas (SRK/T, Barrett Universal II and Hill-RBF) were evaluated. PEX produced statistically significantly higher mean absolute errors and lower percentages of eyes within ± 0.5 D than control eyes in all investigated IOL calculation formulas. There were no statistically significant differences in the median absolute errors between the 3 formulas in either PEX or control eyes. Refractive outcomes after cataract surgery are statistically significantly worse in PEX than in control eyes. All three IOL calculation formulas produced similar results in both PEX and control eyes.Trial registration: ClinicalTrials.gov registration number NCT04783909.

One-year outcomes of microshunt implantation in pseudoexfoliation glaucoma.

PURPOSE: To compare the safety and efficacy of microshunt implantation augmented with Mitomycin C in patients with pseudoexfoliation glaucoma (PEXG) and primary open-angle glaucoma (POAG). METHODS: In this retrospective, single centre, interventional study, 46 eyes of 41 patients with PEXG (20 eyes) and POAG (26 eyes) underwent microshunt implantation. Definition of failure was an intraocular pressure (IOP) lower than 5 or higher than 17mmHg on two consecutive visits, an IOP reduction lower than 20% on two consecutive visits, the need of surgical revisions or reoperations or loss of light perception. Outcome was rated as complete success if achieved without medication, otherwise as qualified success. Furthermore, postoperative complications and interventions were compared between the two groups. RESULTS: Patient demographics were similar, except for older age in the PEXG group (70.9±8.6 versus 77.6±8; p = 0.02). Mean IOP dropped from 21.5±5.8mmHg (PEXG) and 18.2±4.5mmHg (POAG) at baseline to 12.8±3.0mmHg (p<0.0001) and 12.9±4.2mmHg (p<0.0001), respectively, at one year. Mean number of medications were reduced from 2.8±1.3 to 0.3±0.8 for PEXG patients (p<0.0001) and from 2.7±1.3 to 0.3±0.8 for POAG patients (p<0.0001). At one year of follow-up 75.0% of PEXG patients achieved complete success and 80.0% qualified success. In the POAG group rates were 73.1% and 76.9%, respectively. Postoperative complications were comparable between both groups, except for higher rates of hypotony (p = 0.04) and choroidal detachment (p = 0.03) in the PEXG group. CONCLUSION: Microshunt implantation demonstrated similar efficacy results in PEXG and POAG eyes at a follow-up of 12 months. Higher rates of transient hypotony and choroidal detachment were observed in PEXG eyes.

The haplotype of the CDKN2B-AS1 gene is associated with primary open-angle glaucoma and pseudoexfoliation glaucoma in the Caucasian population of Central Russia.

PURPOSE: To replicate the finding of the association of five CDKN2B-AS1 gene polymorphisms (rs7865618, rs1063192, rs944800, rs2157719, and rs4977756) with primary open-angle glaucoma (POAG) and to analyze them for possible association with pseudoexfoliation glaucoma (PXFG) in a Caucasian population of Central Russia. METHODS: A total of 932 participants of Russian ethnicity (self-reported), including 328 patients with PXFG, 208 patients with POAG (high-tension glaucoma), and 396 controls, were enrolled in the study. The SNPs were analyzed for possible associations using logistic regression. RESULTS: Several haplotypes based on the studied SNPs were associated with POAG (three haplotypes) and PXFG (six haplotypes). Haplotype AAAGG of loci rs1063192-rs7865618-rs2157719-rs944800-rs4977756 conferred the highest risk for both POAG (OR = 3.99, рperm = 0.001) and PXFG (OR = 2.84, рperm = 0.001). CONCLUSIONS: The CDKN2B-AS1 gene was associated with an increased risk of both POAG and PXFG in Caucasians of Central Russia. The gene may be related to the development of various types of glaucoma.

Evaluation of the Vestibulocochlear System in Patients with Pseudoexfoliation Syndrome

Objectives: Patients with pseudoexfoliation syndrome (PES) can also have sensorineural hearing loss as well as balance problems. Our aim was to evaluate vestibulocochlear system involvement in PES patients. Materials and Methods: The study included 16 subjects with PES (study group) with a mean age of 66.12±5.64 years and 17 healthy subjects (control group) with a mean age of 61.70±8.46 years. Both groups underwent ophthalmological, neuro-otological, audiological, and vestibular evaluation. Pure-tone audiometry and tympanometry were performed as audiological tests and bithermal caloric test and vestibular-evoked myogenic potential (VEMP) testing were used as vestibular tests. The Romberg, tandem Romberg, and Unterberger tests were also performed. Results: In the PES group, bithermal caloric tests revealed right canal paresis in 6 patients, left canal paresis in 3 patients, and bilateral stimulation loss in 2 patients, despite no clinical evidence of balance loss. Paresis was not detected in any of the control subjects. Unilateral VEMP responses could not be obtained in 3 patients in the PES group. The ocular PES patients whose VEMP waves were obtained differed significantly from the control group (p<0.05). In office tests for vestibular evaluation, pathologic findings were found in 7 of 16 patients in the study group and only 4 subjects in the control group. Audiological evaluation with pure-tone thresholds revealed sensorineural decline at 4000 and 8000 Hertz in the PES patients. A statistically significant difference was found between the study group and the control group (p<0.05). Conclusion: Patients with PES showed elevation in pure-tone thresholds and a decrease in superior and inferior vestibular nerve function, demonstrating that the vestibular system as well as the auditory system are affected in PES.

Pseudoexfoliation syndrome in a 27-year-old patient: a case report / Síndrome de pseudoexfoliação em paciente de 27 anos: relato de caso

ABSTRACT Pseudoexfoliation syndrome is more frequent in people aged >50 yeears, and its prevalence increases with age. Few reports have described cases in younger patients, all with a history of ocular surgery, especially iris resection. Herein, we describe the case of a 27-year old man with bilateral advanced glaucoma and pseudoexfoliation material in OS. He had undergone cataract surgeries OU and a penetrating keratoplasty OD during childhood. Currently, he presented with an intraocular pressure of 40 mmHg OU. The OS showed a white flaky material in the pupillary rim and anterior capsule and a Sampaolesi line as a gonioscopic finding. Trabeculectomy was performed OU, and intraocular pressure control was achieved. Unlike other previously reported cases, this patient did not present any apparent iris manipulation in the affected eye. However, he did undergo an iridectomy in the contralateral eye. This is also the first case to be accompanied by bilateral glaucoma at the time of detection of the pseudoexfoliation material.(AU)

RESUMO A síndrome de pseudoesfoliação é mais frequente em pessoas com mais de 50 anos e sua prevalência aumenta com a idade. Poucos relatos descrevem casos em pacientes mais jovens, todos com história de cirurgia ocular, especialmente ressecção da íris. Descrevemos o caso de um homem de 27 anos com glaucoma bilateral avançado e material de pseudoesfoliação no OE. O paciente foi submetido a cirurgias de catarata em AO e a uma ceratoplastia penetrante no OD durante a infância. Atualmente, ele apresentou PIOs de 40 mmHg em AO. O OE apresentou material escamoso branco na borda pupilar e cápsula anterior, e linha Sampaolesi como achado gonioscópico. A trabeculectomia foi realizada em AO e obteve-se o controle da pressão intraocular. Diferentemente de outros casos relatados, o paciente não apresentou qualquer manipulação aparente da íris no olho afetado. No entanto, ele foi submetido a uma iridectomia no olho contralateral. Além disso, este é o primeiro caso a ser acompanhado de glaucoma bilateral no momento da detecção do material de pseudoesfoliação.(AU)

Intracapsular hemorrhage in the setting of pseudoexfoliation syndrome.

We report the case of an 84-year-old man who presented with decreased vision in his left eye. Ocular history included bilateral pseudoexfoliative glaucoma and vitelliform macular dystrophy. He had undergone intraocular lens placement in both eyes 6 years before presenting at our institution. Over follow-up of 4 years, he experienced recurrent spontaneous hyphema and continued residual intracapsular hemorrhage. He was eventually diagnosed with uveitis-glaucoma-hyphema syndrome in the setting of pseudoexfoliation.

Correlation of the intronic LOXL1 polymorphism rs11638944 with pseudoexfoliation syndrome and glaucoma in a Greek population.

BACKGROUND: The purpose of this study is the development and validation of a novel and robust genotyping method for a new lysyl oxidase-like 1 (LOXL1) intronic polymorphism (rs11638944, C > G) and the investigation of its potential association with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) in a Greek population. MATERIAL AND METHODS: 242 DNA samples from 49 PXS, 64 PXG, 50 primary open-angle glaucoma (POAG) patients and 79 healthy age-matched controls were analyzed. Novel methodologies were developed and optimized, in order to genotype the intronic LOXL1 polymorphism: a) a real-time qPCR and melting curve analysis in the Light Cycler platform for rapid and cost-effective analysis and, b) a conventional PCR-RFLP method for analysis of a small number of samples. In selected samples, validity was checked with the reference DNA Sequencing method. RESULTS: The real-time qPCR methodology was reliable, demonstrating good efficiency, reproducibility, accuracy in genotyping (100% concordance with the PCR-RFLP method and DNA Sequencing), with good allele discrimination (Tm = 53.26°C for C allele, Tm = 61.83°C for G allele, ΔTm = 8.57°C). The results were characterized by Hardy-Weinberg equilibrium in all groups. An increase from 18% in healthy controls to 61% in PXS patients was detected for the G/G homozygote thus, the C allele is protective for PXS with OR = 0.22 (95%CI: 0.11-0.42, p < .0001). Moreover, an increase from 18% in healthy controls to 70% in PXG patients was detected for the G/G homozygote thus, the C allele is protective for PXG with OR = 0.13 (95%CI: 0.06-0.25, p < .0001). CONCLUSIONS: A statistically significant association was verified for the intronic LOXL1 polymorphism rs11638944 and PXS/PXG in a Greek population.

Refractive precision in uncomplicated eyes with pseudoexfoliation: three-piece versus one-piece intraocular lens implantation.

PURPOSE: To evaluate the refractive precision of three-piece versus one-piece intraocular lenses (IOLs) in eyes with pseudoexfoliation (PXF) and changes in anterior chamber depth (ACD) following cataract surgery. METHODS: This prospective, nonrandomized, interventional, comparative case series included PXF eyes, which were implanted with one-piece acrylic IOL or three-piece acrylic IOLs (Group A; n = 31, Group B; n = 30). Non-PXF control eyes were implanted with one-piece acrylic IOL (Group C; n = 30). Postoperative refractive error (RE) and absolute RE, as well as pre- to postoperative ACD changes, were statistically analysed. A p value < 0.05 was considered statistically significant. RESULTS: Changes in ACD (mean ± standard deviation) in Groups A, B and C were 0.9 ± 0.4, 1.0 ± 0.3 and 0.7 ± 0.4 mm, respectively. Significant differences were found between Groups A and C (p = 0.043) and between Groups B and C (p = 0.008). In Groups A, B and C, the median and interquartile (Q1 to Q3) values were 0.3 (-0.8 to 1.0), -0.5 (-0.8 to -0.3) and 0.1 (-0.4 to 0.3) for RE and 1.0 (0.4 to 1.3), 0.5 (0.3 to 0.8) and 0.3 (0.3 to 0.5) for absolute RE, respectively. The RE differences between Group A and B (p = 0.009) and Group B and C (p < 0.001) were statistically significant. For absolute RE, the differences were significant for all comparisons (p < 0.05). CONCLUSION: Refractive precision in PXF eyes may be better with three-piece than with one-piece IOL implantation, but worse than with one-piece IOL implantation in non-PXF eyes. Significant changes in ACD in PXF eyes may be related to RE.

One-year results of gonioscopy-assisted transluminal trabeculotomy: Evaluation of prognostic factors.

PURPOSE: To present the results and complications of gonioscopy-assisted transluminal trabeculotomy in adults with open-angle glaucoma using our different approaches during and after surgery. METHOD: A retrospective comparative study was designed. Patients with regular 12-month follow-up history were included. Two groups were defined: group 1 comprised patients with open-angle glaucoma who underwent gonioscopy-assisted transluminal trabeculotomy surgery alone; group 2 included patients with open-angle glaucoma who underwent combined gonioscopy-assisted transluminal trabeculotomy and cataract extraction. A 30% reduction in preoperative intraocular pressure or postoperative intraocular pressure below 18 mm Hg was considered as surgical success. The success rate, alteration in intraocular pressure, alteration in best-corrected visual acuity, alteration in the need for antiglaucomatous medications, surgical complications, and the need for additional glaucoma surgery were evaluated and compared between the groups. Multivariate logistic regression analysis was used to show the association between the surgical success and possible prognostic factors. RESULTS: A total of 37 eyes fulfilled the inclusion criteria and were analyzed in this study. An overall mean decrease in intraocular pressure of 11.3 ± 9.3 mm Hg was shown at 12 months (p < 0.001). The medication-free surgical success rate was 37.8% (14/37), and the surgical success rate with medication was 91.8% (33/37) at 12 months. Surgical outcomes were similar between patients who underwent gonioscopy-assisted transluminal trabeculotomy alone and those who had combined gonioscopy-assisted transluminal trabeculotomy and cataract extraction (p > 0.05). The most common postoperative complication was hyphemia (89.1%). There were no complications that threatened best-corrected visual acuity. Multivariate logistic regression analysis revealed one significant association between the presence of blood in Schlemm's canal and surgical success (odds ratio = 1.47; 95% confidence interval = 1.25-1.68; p = 0.047). CONCLUSION: This study showed that the gonioscopy-assisted transluminal trabeculotomy procedure is an effective and minimally invasive form of glaucoma surgery. Its effect was related to intraoperative blood in Schlemm's canal.

Two-year outcomes of minimally invasive XEN Gel Stent implantation in primary open-angle and pseudoexfoliation glaucoma.

PURPOSE: The aim of this study was to evaluate the efficacy of XEN® Gel Stent implantation in the treatment of primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (XFG) regarding the reduction of intraocular pressure (IOP) and number of IOP-lowering medications over 2 years. METHODS: In this retrospective, observational, single-centre study, patients with POAG or XFG underwent implantation of the XEN® Gel Stent with or without combined phacoemulsification. Changes in mean IOP, mean number of IOP-lowering medications, number of postoperative interventions, complete or qualified surgical success rate (defined as IOP < 18 mmHg without or with IOP-lowering medication, respectively) and complete surgical failure rate (defined as the necessity of a glaucoma-related secondary surgical intervention or loss of light perception) were assessed 12 months (12M) and 24 months (24M) postoperatively. RESULTS: Seventy-nine eyes of 63 patients with open-angle glaucoma were included in the study (71% POAG, 29% XFG). Before surgery, mean IOP was 23.4 ± 7.9 mmHg. IOP was 14.6 ± 3.6 mmHg 12 months postoperatively (-31% from baseline, 95% CI -42% to -20%, n = 30, p < 0.001) and 14.8 ± 4.4 mmHg 24 months postoperatively (-29% from baseline, 95% CI -30% to -41%, n = 28, p < 0.001). Mean number of IOP-lowering medications was significantly reduced from 2.7 ± 1.1 before surgery to 1.0 ± 1.2 (-69%, 95% CI -89% to 46%, p < 0.001) 12 months after surgery and 1.0 ± 1.2 (-64%, 95% CI -91% to -36%, p < 0.001) at 24 months after surgery. Complete surgical success was achieved in 39% (12M) and 34% (24M) of patients and qualified success in 29% (12M) and 27% (24M). 13 (16%) eyes were classified as complete surgical failure. In 62% of the patients needling procedures had to be performed. CONCLUSION: The XEN® Gel Stent is an efficacious minimal invasive glaucoma surgery for primary open-angle and pseudoexfoliation glaucoma, resulting in significant reduction of IOP and a reduction in glaucoma medications from baseline in two-third of treated patients with 2-year follow-up. Frequent follow-up examinations were mandatory to identify early and late bleb failure and additional needling procedures were necessary to reestablish aqueous flow.

Outcomes of gonioscopy-assisted transluminal trabeculotomy in pseudoexfoliative glaucoma: 24-month follow-up.

AIM: To report on outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with pseudoexfoliative glaucoma (PXG). METHODS: Prospective, interventional, non-comparative case series. A total of 103 eyes from 84 patients with PXG were enrolled to undergo a 360-degree ab interno trabeculotomy with gonioscopic assistance using either a 5.0 polypropylene suture or an illuminated microcatheter with up to 24 months of follow-up. Main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, success rate (IOP reduction ≥20% from baseline or IOP between 6 and 21 mm Hg, without further glaucoma surgery) and complication rate. RESULTS: Mean preoperative IOP was 27.1 mm Hg (95% CI 25.5 to 28.7) using 2.9 (SD 1.1) glaucoma medications which decreased postoperatively to 13.0 mm Hg (95% CI 11.5 to 14.4) and 1.0 (SD 1.1) medications at 24 months (p<0.001). Success rate was 89.2% at 24 months of follow-up, and complication rate was 2.9%. CONCLUSION: At 24 months of follow-up, our results for GATT in PXG demonstrate that this conjunctival sparing procedure effectively lowers IOP and reduces the medications with a low complication rate, in this relatively aggressive glaucoma subtype.

Canaloplasty with Suprachoroidal Drainage in Patients with Pseudoexfoliation Glaucoma - Four Years Results.

Purpose: To evaluate the long-term efficacy and safety of the modified canaloplasty technique with additional suprachoroidal drainage in patients with pseudoexfoliation glaucoma. Methods: This retrospective clinical trial included 131 patients with pseudoexfoliation glaucoma who underwent canaloplasty with suprachoroidal drainage (scD). One hundred and eleven of 131 patients underwent the follow-up examination after 48 months. Primary endpoints were the pressure-lowering and drug-sparing effect as well as the success rates. Secondary endpoints were intra- and postoperative complications and the occurrence of secondary surgical interventions. Results: The IOP was reduced by 45.8% after 12 months (from baseline 23.4 ± 5.1 mmHg to 12.7 ± 2.2 mmHg) and by 45.1% after four years (12.8 ± 2.2 mmHg) (p < .001). The mean number of IOP-lowering medication decreased significantly from 3.4 at baseline to 0.6 after 12 months and to 1.0 after four years. The IOP-reducing effect was even stronger in those cases in whom canaloplasty+ scD was combined with cataract surgery (49.4% after 12 months and 47.6% after four years). No serious complications were observed. Conclusions: The modified surgery technique of canaloplasty with suprachoroidal drainage is a safe and effective way of reducing IOP in patients with pseudoexfoliation glaucoma.

Evaluation of Diurnal Fluctuation in Parafoveal and Peripapillary Vascular Density Using Optical Coherence Tomography Angiography in Patients with Exfoliative Glaucoma and Primary Open-Angle Glaucoma.

PURPOSE: To determine the diurnal variations in parafoveal and peripapillary vessel density using optical coherence tomography angiography in patients with exfoliative glaucoma, patients with primary open-angle glaucoma and healthy individuals. MATERIALS AND METHODS: In this prospective cross-sectional study, 36 exfoliative glaucoma patients, 34 primary open-angle glaucoma patients and 35 healthy individuals were examined. Optical coherence tomography angiography was used for examining the vessel density of peripapillary (radial peripapillary capillary) and parafoveal (superficial layer) regions. Optical coherence tomography angiography readings were obtained at 09:00, 11:00, 14:00 and 16:00 on the same day. Intraocular pressure values were assessed accordingly. The intraclass correlation coefficients were used to evaluate test-retest variability. RESULTS: Diurnal variation in intraocular pressure or vessel density values was not found in any parafoveal or peripapillary region in any of the groups at any hour of measurement. The vessel density in the temporal sector of the exfoliative glaucoma group was significantly lower than in the primary open-angle glaucoma group at all time points. (Mann-Whitney U test; 09:00, P= .015; 11:00, P= .002; 14:00, P= .040; and 16:00, P= .048, respectively). The test-retest repeatability was high and almost excellent for the parafoveal and peripapillary regions in each group (XFG range: 0.757 - 0.985, POAG range: 0.834 - 0.985, and control range: 0.708 - 0.983). CONCLUSIONS: It may be important to estimate the diurnal fluctuation occurring in retinal haemodynamics in patients with exfoliative glaucoma and primary open-angle glaucoma despite the lack of any considerable variation in intraocular pressure and retinal vessel density values in one day. The study found that at any point of time, vessel density of radial peripapillary capillary in temporal region was lower in exfoliative glaucoma patients than in primary open-angle glaucoma patients having the same glaucoma severity.

Pseudoexfoliation syndrome and glaucoma: from genes to disease mechanisms.

PURPOSE OF REVIEW: The genetic basis of pseudoexfoliation (PEX) syndrome, the most common identifiable cause of open-angle glaucoma, is steadily being elucidated. This review summarizes the recent advances on genetic risk factors for PEX syndrome/glaucoma and their potential functional implications in PEX pathophysiology. RECENT FINDINGS: As of today, seven loci associated with the risk of PEX surpassing genome-wide significance have been identified by well-powered genome-wide association studies and sequencing efforts. LOXL1 (lysyl oxidase-like 1) represents the major genetic effect locus, although the biological role of common risk variants and their reversed effect in different ethnicities remain an unresolved problem. Rare protein-coding variants at LOXL1 and a single noncoding variant downstream of LOXL1 showed no allele effect reversal and suggested potential roles for elastin homeostasis and vitamin A metabolism in PEX pathogenesis. Other PEX-associated genetic variants provided biological insights into additional disease processes and pathways, including ubiquitin-proteasome function, calcium signaling, and lipid biosynthesis. Gene-environment interactions, epigenetic alterations, and integration of multiomics data have further contributed to our knowledge of the complex etiology underlying PEX syndrome and glaucoma. SUMMARY: PEX-associated genes are beginning to reveal relevant biological pathways and processes involved in disease development. To understand the functional consequences and molecular mechanisms of these loci and to translate them into novel therapeutic approaches are the major challenges for the future.

Automated Evaluation of Parapapillary Choroidal Microvasculature in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

OBJECTIVE: To determine whether parapapillary choroidal microvasculature (PPCMv) density as measured by optical coherence tomography angiography differs between pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG). DESIGN: Cross-sectional study. METHODS: One hundred ninety-two eyes of 120 subjects from 2 academic referral institutions were enrolled. Automated PPCMv density was calculated using custom Matlab software in inner and outer annuli around the optic nerve region in addition to peripapillary superficial vasculature. Linear modeling was used to compare vessel densities among groups. RESULTS: Data from 64 eyes with PXS, 84 eyes with PXG, and 44 eyes healthy control subjects were analyzed. The differences of visual field mean deviation and peripapillary retinal nerve fiber layer thickness among study groups were statistically significant with lower values in PXG eyes compared with the PXS and control groups. Peripapillary superficial retinal vessel densities were significantly reduced in patients with PXG compared with patients with PXS and normal control subjects (all P < .001) without a difference between PXS and control eyes. Customized outer annular PPCMv density in the PXG group with a value of 11.1% (SD 5.1%) was lower than that in PXS with a value of 13.2% (SD 5.3%; P = .001). Similarly, PXS values were lower than those of control eyes with a value of 18.6% (SD 5.1%; P < .001). CONCLUSION: A progressive decrease in outer PPCMv from the control group to those with PXS without glaucoma to those with PXS and glaucoma (PXG) showed deep peripapillary vasculopathy in pseudoexfoliation syndrome. Choroidal vessel density may be affected early in the course of pseudoexfoliation before glaucoma develops.

Peripapillary perfused capillary density in true versus pseudoexfoliation syndrome: An OCTA study.

PURPOSE: To compare peripapillary perfused capillary density (PCD) among eyes with true exfoliation syndrome (TEX), eyes with pseudoexfoliation syndrome (PEX), and healthy control eyes. MATERIALS AND METHODS: In this observational cross-sectional study, eyes with and without TEX or PEX were assessed by optical coherence tomography angiography (OCTA) imaging. Bilateral OCTA images (4.5 × 4.5 mm2) centered at the optic nerve head were obtained using a commercial spectral domain OCTA system. Optic nerve head perfusion was quantified using the split-spectrum amplitude decorrelation angiography algorithm. Categorical and continuous variables were compared using the chi-squared test and one-way analysis of variance, respectively. The generalized estimating equation was used to adjust for confounding factors and determine inter-ocular associations. RESULTS: We enrolled 39 eyes with TEX, 31 eyes with PEX, and 32 control eyes. There were no significant differences among the three groups regarding age, intraocular pressure, cup-to-disc ratio, blood pressure, or axial length (all p>0.05). There were significant differences in global PCD among the three groups (p = 0.01). There were significant differences in annular PCD between the TEX and PEX groups (p = 0.027). CONCLUSIONS: While both global and annular PCDs did not differ between the TEX and control groups, greater loss of annular PCD in the PEX group than in the TEX and control groups suggests more pronounced microvascular disturbance in PEX. SYNOPSIS/PRECIS: Greater microvascular attenuation in PEX compared with TEX and normal control measured by OCTA.

A comparison of the corneal biomechanics in pseudoexfoliation glaucoma, primary open-angle glaucoma and healthy controls using Corvis ST.

PURPOSE: To compare the corneal biomechanical parameters between pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG) and healthy controls using Corvis ST. METHODS: A prospective, cross-sectional study was conducted which included 132 treatment-naïve eyes which underwent Corvis ST. The study cohort comprised of 44 eyes with PXG, 42 eyes with POAG and 46 healthy controls. Corneal biomechanical parameters, which included corneal velocities, length of corneal applanated surface, deformation amplitude (DA), peak distance and radius of curvature, were compared between the groups using analysis of variance models. RESULTS: The 3 groups were demographically similar. The mean IOP was 15.7 ±3 mmHg in the control group, 21.3 ±5 mmHg in the POAG group and 25.8 ±7 mmHg in the PXG group (p<0.0001). Corneal pachymetry was similar across the 3 groups. Mean DA was significantly lower (p<0.0001) in the PXG group (0.86 ±0.18 mm) compared to the POAG group (0.97 ±0.14mm) and the control group (1.10 ±0.15mm). Corneal velocities were also found to be statistically significantly different between the groups. However, after adjusting for IOP, there was no difference in any of the biomechanical parameters between the 3 groups. CONCLUSION: Corneal biomechanical parameters measured on Corvis ST are not different between eyes with PXG, POAG and healthy controls after adjusting for IOP.