Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma.

We investigated optic nerve head factors associated with initial parafoveal scotoma (IPFS) in primary open-angle glaucoma. Eighty (80) patients with an IPFS and 84 patients with an initial nasal step (INS) were compared. Central retinal vascular trunk (CRVT) deviation from the Bruch's membrane opening (BMO) center was measured as a surrogate of lamina cribrosa (LC)/BMO offset, and its obliqueness was defined as the absolute value of angular deviation from the fovea-BMO axis. Proximity of retinal nerve fiber layer defect (RNFLD) was defined as the angular deviation of the inner RNFLD margin from the fovea-BMO axis. Microvasculature dropout (MvD) was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Factors associated with IPFS, as compared with INS, were assessed using logistic regression analyses and conditional inference tree analysis. The IPFS group had more oblique CRVT offset (P < 0.001), RNFLD closer to the fovea (P < 0.001), more MvD (P < 0.001), and more LC defects (P < 0.001) compared to the INS group. In logistic regression analyses, obliqueness of CRVT offset (P = 0.002), RNFLD proximity (P < 0.001), and MvD (P = 0.001) were significant factors influencing the presence of IPFS. Conditional inference tree analysis showed that RNFLD closer to the fovea (P < 0.001) in the upper level, more oblique CRVT offset (P = 0.013) and presence of MvD (P = 0.001) in the lower level were associated with the probability of having IPFS. IPFS was associated with closer RNFLD location to the fovea when assessed from the BMO. Oblique LC/BMO offset may not only mask RNFLD proximity to the fovea due to a deviated funduscopic disc appearance, but also potentiate IPFS via focal LC defect and MvD.

Characteristics of beta parapapillary atrophy in primary angle-closure suspect.

OBJECTIVE: To investigate the characteristics of beta parapapillary atrophy (ß-PPA) in patients with primary angle-closure suspect (PACS). METHODS AND ANALYSIS: In total, 215 and 259 eyes with PACS and non-PACS (NPACS), respectively, were enrolled in this observational, cross-sectional study. Stereoscopic fundus and optical coherence tomography images were used to characterise ß-PPA; the former was also used to measure the major ß-PPA parameters. Univariate and multiple logistic regression analyses were used to identify the factors correlated with the presence of ß-PPA and with ß-PPA parameters. RESULTS: The ß-PPA occurrence rates were 48.80% and 44.40% in the PACS and NPACS groups, respectively, with no significant difference between groups. Compared with that in the NPACS group, the ß-PPA area was significantly larger (p=0.005) in the PACS group, but the angular extent and maximum radial length did not differ between groups (p=0.110 and 0.657, respectively) after adjusting for age and axial length. The presence of ß-PPA was associated with older age (OR 1.057, 95% CI 1.028 to 1.088, p<0.001) and larger disc area (OR 1.716, 95% CI 1.170 to 2.517, p=0.006). A larger ß-PPA area was associated with older age (p=0.014), greater vertical cup-to-disc ratio (p=0.028), larger disc area (p<0.001) and PACS diagnosis (p=0.035). CONCLUSION: 48.80% of participants with PACS had ß-PPA, which is slightly larger than NPACS. The area of ß-PPA was larger in PACS, while the angular extent and maximum radial length did not differ between groups.

Comparison between MIGS with trabeculectomy in the management of open-angle glaucoma with cataract: A systematic review.

Age is an important risk factor for both glaucoma and cataract. As global life expectancy continues to rise, the prevalence of concomitant open-angle glaucoma (OAG) and cataracts is increasing. Currently, there is a lack of definitive consensus on the optimal management approach for such individuals. Conventionally, trabeculectomy (Trab) in combination with phacoemulsification is the preferred method. Recent developments in microinvasive glaucoma surgery (MIGS), which offer similar results with fewer complications, provide a new possible approach to this condition. This study aimed to assess the current knowledge of combination surgery in patients with cataract and OAG to provide a comprehensive understanding and help its implementation in clinical settings. A comprehensive systematic search was conducted in May 2021 on five databases (MEDLINE, Embase, SCOPUS, Proquest, EBSCO, and Cochrane Library). The results were filtered for English and human studies but not publication year. All studies published up to May 2021 were reviewed. Newcastle-Ottawa Scale and PEDro scale were used to screen studies for risk of bias where appropriate. Four studies satisfied the inclusion criteria and were subsequently added in this review. Study designs consisted of one RCT and three descriptive studies. Appropriate assessment tools were used; these studies demonstrated moderate to good quality. Postoperative mean IOP, IOP reduction, and qualified success rates were comparable in the Phaco-MIGS (Phaco-endoscopic cyclophotocoagulation (ECP), Phaco-ab interno trabeculectomy (AIT)) and Phaco-Trab group. Severe complication was reported only in the latter. Phaco-MIGS (in particular, trabectome) shows excellent promise as an option for individuals with OAG and concomitant cataract; further research through RCT is required to validate these findings.

Comparison of bleb morphologies between phacoemulsification combined with Ex-PRESS mini shunt implantation, phacotrabeculectomy and trabeculectomy alone: a two-year retrospective in vivo confocal microscopy study.

BACKGROUND: To compare the bleb morphologies of phacoemulsification combined with Ex-PRESS implantation (Phaco-ExPRESS), phaco trabeculectomy (Phaco-Trab), and trabeculectomy (Trab) in postoperative two years. METHODS: Patients with primary open-angle glaucoma (POAG) with or without cataracts were included in this study. All patients underwent surgeries of either Phaco-ExPRESS, Phaco-Trab, or Trab. The morphologic structures of the filtering bleb, including microcysts area, hyperreflective dot density, and stromal connective tissue under in vivo confocal microscope (IVCM), were compared between the three groups. The data were collected preoperatively and postoperatively at 2 weeks, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months. RESULTS: Eighty-nine eyes from 89 patients were enrolled, including 32 in the Phaco-ExPRESS group, 25 in the Phaco-Trab group, and 32 in the Trab group. In a 24-month follow-up, bleb morphologies in Phaco-ExPRESS were similar to the Trab group. The area of epithelial microcysts was significantly increased in Phaco-ExPRESS and Trab groups while significantly decreased in Phaco-Trab. At postoperative 24 months, the complete success rate was 65.1% in Phaco-ExPRESS, 32.0% in Phaco-Trab, and 59.4% in the Trab group (P = 0.03). The phaco-Trab group had more postoperative anti-glaucoma medications than the other two groups (P < 0.05). CONCLUSIONS: Phaco-ExPRESS group and Trab group had similar blebs morphologies in IVCM, with larger microcyst area, looser connective tissue, and less inflammation than Phaco-Trab, indicating that the function of blebs in the Phaco-ExPRESS and Trab group, was more potent than that of Phaco-Trab. All these surgical methods provided adequate IOP control, but Phaco-Trab required more anti-glaucoma medications.

Visual outcomes after cataract surgery in monocular compared to binocular patients: a case-control study.

PURPOSE: We aimed to identify ocular comorbidities and reasons of blindness in monocular patients and to compare visual outcomes of cataract surgery between monocular and binocular patients. METHODS: A single-center case-control study was conducted between November 2011 and May 2019 to compare consecutive series of patients needing cataract surgery in Strasbourg University Hospitals, France. Cases were patients with permanent monocular vision loss. Controls were binocularly sighted patients. All patients underwent cataract surgery using phacoemulsification technique. Chart analysis included demographic data, medical history, and surgical determinants data. Student's t tests and Fisher's exact tests were the main methods used for statistical analysis. RESULTS: Each group included 80 patients. The mean age at the time of surgery was significantly higher in monocular than binocular patients (77 vs. 71 years, p < 0.001). Thirty-two monocular patients (40%) had ocular comorbidities, compared to only 19 (23%) in the control group (p < 0.05). The leading cause of monocular status was amblyopia caused by strabismus (22 patients, 27.5%). Age-related macular degeneration, open-angle glaucoma, and diabetic retinopathy were the three main ocular comorbidities that were observed in the monocular group. Monocular patients had significantly lower visual acuity than the control group (p < 0.01) before and after cataract surgery. Conversely, improvement in visual acuity after surgery was not statistically different between groups (p = 0.054). There was no statistically significant difference in the rate of surgical complications between groups (p = 0.622). CONCLUSIONS: This study illustrates that cataract surgery in monocular patients is not more complicated than in binocular patients, but that it is significantly delayed.

Clinical outcomes of Ahmed glaucoma valve implantation in primary open-angle glaucoma and pseudoexfoliative glaucoma.

PURPOSE: To investigate the clinical outcomes of Ahmed glaucoma valve (AGV) implantation in primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG). METHODS: The patients who underwent AGV implantation for POAG and PEXG between January 2015 and December 2021 in a single tertiary center eye clinic were reviewed retrospectively. Thirty-one eyes with the diagnosis of POAG constituted Group 1 and 40 eyes with the diagnosis of PEXG constituted Group 2. The primary outcome measures were intraocular pressure (IOP) changes after AGV implantation and surgical success at the last visit. We evaluated complete and qualified surgical success using the following three criteria: (1) IOP ≤ 21mmH g, (2) IOP ≤ 18 mmHg, and (3) IOP ≤ 15 mmHg, as well as the absence of any serious complications, such as light perception loss and phthisis bulbi, and additional de novo glaucoma surgery. RESULTS: The mean follow-up times were 25.2 (± 21.4) months and 27.6 (± 19.8) months for Groups 1 and 2, respectively (p > 0.05). In Groups 1 and 2, the mean preoperative IOPs were 31.9 ± 9.4 mmHg and 32.3 ± 8.4 mmHg, respectively, which significantly reduced to 14.5 ± 0.7 mmHg and 11.6 ± 0.6 mmHg, respectively at the last postoperative visit (p < 0.001 for both). The mean IOP value at the last visit was statistically significantly lower in Group 2 (p = 0.006). At the last visit, the number of eyes with qualified success according to criteria 1, 2, and 3 was 26 (83.9%), 25 (80.6%), and 18 (58.1%), respectively, in Group 1 and 39 (97.5%), 39 (97.5%), and 32 (80%), respectively, in Group 2. The comparison of the qualified success rates showed statistically significantly higher rates in Group 2 for criterion 2 (p = 0.038). CONCLUSION: AGV implantation had high success rates in both POAG and PEXG, but at the final visit, lower IOP levels were reached in the latter.

Epiretinal membrane development after Ex-Press glaucoma filtration device implant: 2-year results of a case control study.

BACKGROUND: The most common retinal complications after glaucoma surgery are choroidal detachment, hypotony maculopathy, malignant glaucoma, vitreous hemorrhage, endophthalmitis and retinal detachment. However, if glaucoma surgery is a risk factor for the ERM development needs to be clarified. This study aims to assess the incidence of epiretinal membrane (ERM) in 2 years of follow-up in patients with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. METHODS: A prospective, consecutive, single-center, case-control study. We enrolled patients affected by POAG and scheduled for Ex-Press device implant with or without concomitant cataract surgery. The control group was the contralateral eyes which continues anti-glaucomatous eyedrops. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography were performed before surgery, at 6 months and 24 months of follow-up. RESULTS: Eighty-two eyes of 41 consecutive patients, 18 males and 23 females with a mean age of 70, 29 ± 8,45, were analyzed at 24 months. 39.1% of eyes developed ERM: 29.3% were cellophane macular reflex (CMR) and 9.8% were pre-macular fibrosis (PMF). In the control group, 19.5% of eyes developed ERM: 17.1% were CMR and 2.4% were PMF. No statistically significant difference was reported (p = 0.121) between treated and control group. ERM development did not affect significantly the central foveal thickness (260.13 ± 35.01 µm at baseline, 265.03 ± 34.90 µm at 6 months and 275.18 ± 33.31 µm at 24 months) and macular volume (7.75 ± 0.43 mm3 at baseline, 7.77 ± 0.48 mm3 at 6 months and 7.77 ± 0.46 mm3 at 24 months), remained comparable to reported average measures in healthy individuals during the follow-up. Concomitant cataract surgery did not increase the ERM incidence. CONCLUSION: Ex-Press implant may increase the ERM incidence regardless concomitant cataract surgery, accelerating or inducing a posterior vitreous detachment, such as other ocular surgical procedure. Nevertheless, the vast majority of ERM are CMR, not affecting the macular profile.

[Primary open angle glaucoma and sleep apnea syndrome: A review of the literature]. / Glaucome primitif à angle ouvert et syndrome d'apnée du sommeil : une revue de la littérature.

The relationship between glaucoma and Obstructive Sleep Apnea Syndrome (OSAS) has long been discussed, with conflicting study findings. OSAS appears in the most recent studies to be more of an aggravating factor than an independent risk factor for glaucoma. Patients with OSAS may develop a more rapid progression of primary open-angle glaucoma (POAG). OSAS may damage the optic nerve not only by increasing the intraocular pressure (IOP) but also by altering the blood supply to the optic nerve as shown by more recent work with OCT-Angiography. Although the systemic benefits of Continuous Positive Airway Pressure (CPAP) have been demonstrated, few studies have evaluated its effect on the optic nerve. CPAP might act on glaucomatous neuropathy by improving the blood supply to the optic nerve. The study of this mechanism of action might provide new insights into the relationship between OSAS and glaucoma.

Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset in the Ocular Hypertension Treatment Study.

Purpose: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). Methods: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. Results: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (>95th percentile or <75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. Conclusions: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting.

Successful resolution of serous macular detachment following glaucoma-filtering surgery alone for acquired optic disc pit maculopathy.

PURPOSE: To describe a case of acquired glaucomatous optic disc pit-related maculopathy successfully treated with glaucoma filtering surgery alone. CASE DESCRIPTION: A 67-year-old male was diagnosed with advanced primary open angle glaucoma in both eyes, with a cup: disc ratio of 0.85 in the right eye and 0.95 in the left eye. Visual acuity at presentation was 20/60, and intraocular pressure was 14 mm Hg in the left eye. The fundus of the left eye revealed a serous macular retinal detachment due to an acquired optic disc pit. RESULTS: The left eye of the patient underwent combined cataract and glaucoma filtering surgery. The serous macular detachment resolved completely 15 months after surgery, with a documented visual acuity of 20/40 and intraocular pressure of 10 mm Hg without the use of additional antiglaucoma medications. There was no recurrence of serous macular detachment even after the two-year follow-up visit. CONCLUSION: This case demonstrates that controlling intraocular pressure alone resulted in complete resolution of serous macular detachment in acquired optic disc pit maculopathy without the need for pars plana vitrectomy.

Prospective, Randomized Controlled Trial of Cataract Surgery vs Combined Cataract Surgery With Insertion of iStent Inject.

PURPOSE: To evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular microbypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. DESIGN: Prospective, randomized, assessor-masked controlled trial at a single centre. PARTICIPANTS: Eyes with visually-significant cataract and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 to 30 mmHg on 0 to 3 ocular hypotensive medications. METHODS: Participants eyes were randomized (2017-2020) 1:1 to combined cataract surgery with iStent Inject (treatment group, n = 56) or cataract surgery alone (control group, n = 48), and followed up for 2 years. MAIN OUTCOME MEASURES: The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24-months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24-months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. RESULTS: Participants (67.3% male) were aged 53 to 85 years, and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2-1.1, P = 0.008). In the treatment group, 57% of eyes were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the 2 groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the 2 groups. The visual outcomes and safety profiles were similar between the 2 groups. CONCLUSIONS: Combined cataract surgery with iStent Inject achieved a clinically- and statistically-significantly greater reduction in ocular hypotensive medication usage at 24-months compared to cataract surgery alone, with no significant difference in IOP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Systemic Diseases in Primary Open-Angle Glaucoma. / Internistische Erkrankungen und Zusammenhang mit dem primären Offenwinkelglaukom.

Primary open-angle glaucoma is a neurodegenerative disease with progressive chronic optic neuropathy and corresponding visual field defects. In this literature review, we discuss systemic diseases and their mechanism for developing glaucoma, including systemic hypertension and hypotension, diabetes, dyslipidemia, obstructive sleep apnoea syndrome, chronic kidney disease, migraine, and polypharmacy.

Outcome of combined trabeculectomy with cataract surgery in patients on prostaglandin analogs and aqueous suppressants.

PURPOSE: To compare the effect of prostaglandin analogs (PGA) against other glaucoma medications (non-PGA) on the intraocular pressure (IOP) outcomes of combined trabeculectomy with phacoemulsification, and the conjunctival cell profile in persons with primary open-angle (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS: A prospective cohort study was conducted among 116 patients with POAG or PXFG on glaucoma medications for a minimum of 3 months undergoing glaucoma triple procedure. Patients were divided into two groups (PGA and non-PGA) based on preoperative exposure to PGA. IOP outcomes were assessed for up to 2 years. Conjunctival biopsy specimens were obtained at the time of surgery, and histopathological analysis was performed. RESULTS: Forty-two patients were in the PGA group, 67 were in the non-PGA group, and seven were lost to follow-up. The non-PGA group had lesser mean postoperative IOP and needed fewer postoperative medications compared to the PGA group in all visits up to 2 years. The non-PGA group had better complete success rate (50.7% vs. 14.3%, P < 0.001). Kaplan-Meier survival estimates showed a significant difference in cumulative complete success rate between non-PGA (67%) and PGA (26%) by 24 months ( P < 0.001). The Cox proportional model showed the type of drug to be significantly associated with surgical failure. Histopathological analysis revealed that the PGA group had higher numbers for each type of inflammatory cell (except mast cells) compared to the non-PGA group. CONCLUSION: Patients on PGA are likely to have a higher postoperative IOP and may need more medications for IOP control after a glaucoma triple procedure.

Effect of Preoperative Trabecular Meshwork Pigmentation and Other Eye Characteristics on Outcomes of Combined Phacoemulsification/Minimally Invasive Glaucoma Surgery.

PURPOSE: To investigate associations between pigmentation of the trabecular meshwork (PTM) and other preoperative eye characteristics and outcomes of minimally invasive glaucoma surgery combined with phacoemulsification (Phaco/MIGS). DESIGN: Retrospective interventional case series. PARTICIPANTS: Academic glaucoma clinic patients with symptomatic cataract and glaucoma treated with combined Phaco/MIGS. METHODS: Analyzing preoperative PTM, intraocular pressure (IOP), IOP-lowering medications and visual acuity (VA) data in relation to Phaco/MIGS outcomes. MAIN OUTCOME MEASURES: Pigmentation of the trabecular meshwork and other preoperative eye characteristics in relation to Phaco/MIGS success defined as postoperative IOP between 5 and 21 mmHg and IOP reduction of ≥ 20% and/or a reduction of ≥ 1 IOP-medications compared to baseline, and final IOP, IOP-lowering medications and VA. RESULTS: A total of 265 eyes (172 patients, mean age, 73.5 [standard deviation, 10.0], range 35-95 years, male 40.0%) were identified and categorized with high PTM (108 eyes, 40.8%) or low PTM (157 eyes, 59.2%). The high PTM group, compared with the low PTM group, demonstrated higher preoperative IOP (16.7 [standard error 0.4] vs. 15.2 [0.4] mmHg, P = 0.009), included more eyes with primary open-angle glaucoma (POAG, P = 0.03), fewer eyes with normal-tension glaucoma (NTG, P = 0.01), and fewer eyes with mild stage glaucoma (P = 0.001). Compared to baseline, final IOP decreased by 6.5 [2.4]% and 13.4 [3.0]% (P = 0.075) to 13.5 [0.3] mmHg and 13.6 [0.4] mmHg (P = 0.77) in the low and high PTM groups, respectively, and IOP-lowering medications decreased by 34.6 [4.9]% (n = 116) and 18.1 [7.3]% (n = 85), respectively (P = 0.062). Surgical success was 59.9% and 58.3%, respectively (P = 0.87). It was positively associated with higher preoperative IOP (hazard ratio 1.08 [95% confidence interval 1.04-1.12] P < 0.0001) and higher number of preoperative IOP-medications (1.20 [1.05-1.37] P = 0.007), negatively associated with history of selective laser trabeculoplasty (SLT, 0.40 [0.23-0.68] P = 0.0009) and longer axial length (0.87 [0.80-0.94], P = 0.0006), but was not associated with PTM. CONCLUSIONS: Higher PTM was associated with POAG rather than NTG, with more severe glaucoma and higher preoperative IOP, but not with Phaco/MIGS success. Surgical success was positively associated with higher preoperative IOP and number of IOP-medications and negatively associated with history of SLT and longer axial length. These findings may help guide glaucoma surgeons in surgical planning and patient counseling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Differentiating stages of functional vision loss from glaucoma using the Disc Damage Likelihood Scale and cup:disc ratio.

BACKGROUND: Glaucoma staging is critical for treatment planning but has rarely been tested in severe/end-stage disease. We compared the performance of the Disc Damage Likelihood Scale (DDLS) and cup:disc ratio (CDR) using a functional glaucoma staging system (GSS) as the reference standard. METHODS: Post hoc analysis of a randomised controlled trial at the Eye Department of Kilimanjaro Christian Medical Centre, Tanzania. Eligible participants (aged ≥18 years) with open-angle glaucoma, intraocular pressure (IOP) of >21 mm Hg, were randomised to timolol 0.5% eye drops or selective laser trabeculoplasty. Fundoscopy established vertical and horizontal CDRs and DDLS. Visual acuity and static visual fields were graded (GSS). The study used area under the receiver operating characteristic (AROC) curves and Spearman's rank correlation coefficients to compare staging systems. Logistic regression with generalised estimating equations determined risk factors of functional severe/end-stage glaucoma. RESULTS: 382 eyes (201 participants) were evaluated; 195 (51%) had severe or end-stage glaucoma; mean IOP was 26.7 (SD 6.9) mm Hg. DDLS yielded an AROC of 0.90 (95% CI 0.87 to 0.93), vertical cup:disc ratio (vCDR) of 0.88 (95% CI 0.85 to 0.91, p=0.048) for identifying severe/end-stage disease. Correlation coefficients comparing GSS to DDLS and vCDRs were 0.73 and 0.71, respectively. Advanced structural stages, vision impairment, higher IOP and less financial resources were risk factors of functional severe/end-stage glaucoma. CONCLUSION: This study indicates that both structural staging systems can differentiate severe/end-stage glaucoma from less severe disease, with a moderate advantage of DDLS over CDR. Clinical examination of the optic disc plays an important role in addition to functional assessment when managing severe/end-stage glaucoma.

Central visual field damage in glaucoma eyes with choroidal microvasculature dropout with and without high axial myopia.

PURPOSE: To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia. DESIGN: Cross-sectional study. METHODS: Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images. RESULTS: Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm2 vs 0.31 (0.19, 0.42) mm2, p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD. CONCLUSIONS: MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects.

Progressive Macular Vessel Density Loss and Visual Field Progression in Open-angle Glaucoma Eyes with Central Visual Field Damage.

PURPOSE: To investigate the association between the longitudinal changes in both macular vessel density (mVD) and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and visual field (VF) progression (including central VF progression) in open-angle glaucoma (OAG) patients with central visual field (CVF) damage at different glaucoma stages. DESIGN: Retrospective longitudinal study. PARTICIPANTS: This study enrolled 223 OAG eyes with CVF loss at baseline classified as early-to-moderate (133 eyes) or advanced (90 eyes) stage based on the VF mean deviation (MD) (-10 dB). METHODS: Serial mVDs at parafoveal and perifoveal sectors and mGCIPLT measurements were obtained using OCT angiography and OCT during a mean follow-up of 3.5 years. Visual field progression was determined using both the event- and trend-based analyses during follow-up. MAIN OUTCOME MEASURES: Linear mixed-effects models were used to compare the rates of change in each parameter between VF progressors and nonprogressors. Logistic regression analyses were performed to determine the risk factors for VF progression. RESULTS: In early-to-moderate stage, progressors showed significantly faster rates of change in the mGCIPLT (-1.02 vs. -0.47 µm/year), parafoveal (-1.12 vs. -0.40%/year), and perifoveal mVDs (-0.83 vs. -0.44%/year) than nonprogressors (all P < 0.05). In advanced stage cases, only the rates of change in mVDs (parafoveal: -1.47 vs. -0.44%/year; perifoveal: -1.04 vs. -0.27%/year; all P < 0.05) showed significant differences between the groups. By multivariable logistic regression analyses, the faster rate of mVD loss was a predictor of VF progression regardless of glaucoma stage, while the rate of mGCIPLT loss was significantly associated with VF progression only in early-to-moderate stage cases. CONCLUSIONS: Progressive mVD loss is significantly associated with VF progression (including central VF progression) in the OAG eyes with CVF loss regardless of the glaucoma stage. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Impact of Type 2 diabetes mellitus and insulin use on progression to glaucoma surgery in primary open angle glaucoma.

PURPOSE: To investigate outcomes of primary open-angle glaucoma (POAG) patients with and without type 2 diabetes mellitus (T2DM). METHODS: Retrospective observational study using U.S. nationwide healthcare insurance claims database. Patients ≥40 years old with at least one HbA1c within one year of POAG diagnosis were included. Diabetic factors associated with POAG progression requiring glaucoma surgery were evaluated using multivariable Cox proportional hazards regression models adjusted for demographic, diabetic and glaucoma factors. T2DM diagnosis and use of either oral hypoglycaemic agents or insulin therapy were assessed in association with POAG progression requiring glaucoma surgery. RESULTS: 104,515 POAG patients were included, of which 70,315 (67%) had T2DM. The mean age was 68.9 years (Standard deviation 9.2) and 55% were female. Of those with T2DM, 93% were taking medication (65,468); 95% (62,412) taking oral hypoglycaemic agents, and 34% (22,028) were on insulin. In multivariable analyses, patients with T2DM had a higher hazard of requiring glaucoma surgery (Hazard ratio, HR 1.15, 95% CI 1.09-1.21, p < 0.001). Higher mean HbA1c was also a significant predictor of progression requiring glaucoma surgery (HR 1.02, 95% CI 1.01-1.03, p < 0.001). When evaluating only patients who were taking antidiabetic medication, after adjusting for confounders, insulin use was associated with a 1.20 higher hazard of requiring glaucoma surgery compared to oral hypoglycaemic agents (95% CI 1.14-1.27, p < 0.001), but when stratified by HbA1c, this effect was only significant for those with HbA1c > 7.5%. CONCLUSIONS: Higher baseline HbA1c, particularly in patients taking insulin may be associated with higher rates of glaucoma surgery in POAG.

Secondary glaucoma: Toward interventions based on molecular underpinnings.

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.