Future directions of glaucoma treatment: emerging gene, neuroprotection, nanomedicine, stem cell, and vascular therapies.

PURPOSE OF REVIEW: The aim of this article is to summarize current research on novel gene, stem cell, neuroprotective, nanomedicine, and vascular therapies for glaucoma. RECENT FINDINGS: Gene therapy using viral vectors and siRNA have been shown to reduce intraocular pressure by altering outflow and production of aqueous humor, to reduce postsurgical fibrosis with few adverse effects, and to increase retinal ganglion cell (RGC) survival in animal studies. Stem cells may treat glaucoma by replacing or stimulating proliferation of trabecular meshwork cells, thus restoring outflow facility. Stem cells can also serve a neuroprotective effect by differentiating into RGCs or preventing RGC loss via secretion of growth factors. Other developing neuroprotective glaucoma treatments which can prevent RGC death include nicotinamide, the NT-501 implant which secretes ciliary neurotrophic factor, and a Fas-L inhibitor which are now being tested in clinical trials. Recent studies on vascular therapy for glaucoma have focused on the ability of Rho Kinase inhibitors and dronabinol to increase ocular blood flow. SUMMARY: Many novel stem cell, gene, neuroprotective, nanomedicine, and vascular therapies have shown promise in preclinical studies, but further clinical trials are needed to demonstrate safety and efficacy in human glaucomatous eyes. Although likely many years off, future glaucoma therapy may take a multifaceted approach.

A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease.

Aim: To investigate the limitations of diagnosing glaucoma in patients with coexistent neurodegenerative disease (NDD) by collecting information on demographics, examination findings, optical coherence tomography (OCT), and visual field (VF) tests. Materials and methods: Retrospective cohort study of patients with primary open-angle glaucoma and coexistent dementia, multiple sclerosis (MS), Parkinson's disease (PD), or cerebrovascular accident (CVA) from 2014 to 2020. We included patients with a minimum of 3 years of follow-up. Demographics, ophthalmic exam, OCT, and VF findings were reported and compared across NDD groups using the Chi-squared and analysis of variance tests. Results: We included 199 patients with glaucoma and coexistent NDD, including dementia (51.3%), CVA (11.2%), PD (18.1%), and MS (19.6%). Cupping, neuroretinal rim thinning, pallor, and peripapillary atrophy of the optic nerve were most frequently observed. There was a high number of missing values from OCT to VF tests, and zero patients had a complete OCT or VF test. Additionally, 67.8 and 77.4% of patients received <1 OCT and VF/year, respectively. Retinal nerve fiber layer (RNFL) thinning was observed most frequently in the superior (33.2% OD and 30.7% OS) and inferior (25.6% OD and 30.2% OS) quadrants, with the most significant thinning seen in CVA patients compared to other NDDs (p < 0.05). Glaucoma hemifield tests (GHTs) were abnormal in 23.1% OD and 22.6% OS, and the average mean deviation was -7.43 [standard deviation (SD) 8.23] OD and -8.79 (SD 7.99) OS. Conclusion: The OCT and VF tests are frequently unavailable and may be confounded in patients with coexistent glaucoma and NDDs, complicating glaucoma diagnosis and management. Clinical significance: Diagnosing and managing glaucoma in patients with coexistent NDD is difficult, given the lack of available and reliable OCT and VF testing data. Providers may be forced to rely on intraocular pressure (IOP) and other imperfect measures. How to cite this article: Ciociola EC, Patel K, Blahnik T, et al. A Retrospective Cohort Study on the Difficulties of Diagnosing and Managing Glaucoma in Patients with Coexistent Neurodegenerative Disease. J Curr Glaucoma Pract 2023;17(3):126-133.

Decision Factors for Glaucoma Suspects and Ocular Hypertensive Treatment at an Academic Center.

Aims and background: Practice guidelines assert that high-risk glaucoma suspects should be treated. Yet, there is ambiguity regarding what constitutes a high enough risk for treatment. The purpose of this study was to determine which factors contribute to the decision to treat glaucoma suspects and ocular hypertensive patients in an academic ophthalmology practice. Materials and methods: Retrospective cohort study of glaucoma suspects or ocular hypertensives at an academic ophthalmology practice from 2014 to 2020. Demographics, comorbidities, intraocular pressure (IOP), optical coherence tomography (OCT) findings, and visual field measurements were compared between treated and untreated patients. A multivariable logistic regression model assessed predictors of glaucoma suspected treatment. Results: Of the 388 patients included, 311 (80%) were untreated, and 77 (20%) were treated. There was no statistical difference in age, race/ethnicity, family history of glaucoma, central corneal thickness (CCT), or any visual field parameters between the two groups. Treated glaucoma suspects had higher IOP, thinner retinal nerve fiber layers (RNFL), more RNFL asymmetry, thinner ganglion cell-inner plexiform layers (GCIPL), and a higher prevalence of optic disc drusen, disc hemorrhage, ocular trauma, and proliferative diabetic retinopathy (PDR) (p < 0.05 for all). In the multivariable model, elevated IOP {odds ratio [OR] 1.16 [95% confidence interval (CI) 1.04-1.30], p = 0.008}, yellow temporal [5.76 (1.80-18.40), p = 0.003] and superior [3.18 (1.01-10.0), p = 0.05] RNFL quadrants, and a history of optic disc drusen [8.77 (1.96-39.34), p = 0.005] were significant predictors of glaucoma suspect treatment. Conclusion: Higher IOP, RNFL thinning, and optic disc drusen were the strongest factors in the decision to treat a glaucoma suspect or ocular hypertensive patient. RNFL asymmetry, GCIPL thinning, and ocular comorbidities may also factor into treatment decisions. Clinical significance: Understanding the clinical characteristics that prompt glaucoma suspect treatment helps further define glaucoma suspect disease status and inform when treatment should be initiated. How to cite this article: Ciociola EC, Anderson A, Jiang H, et al. Decision Factors for Glaucoma Suspects and Ocular Hypertensive Treatment at an Academic Center. J Curr Glaucoma Pract 2023;17(3):157-165.

A Pilot Study Assessing Treatment Outcomes in Neovascular Glaucoma Using Ahmed Glaucoma Valve with and without Cyclophotocoagulation.

Purpose: The purpose of this retrospective pilot study was to examine the short-term effect of simultaneous Ahmed Glaucoma Valve implantation and cyclophotocoagulation on postoperative outcomes in patients with neovascular glaucoma. Methods and materials: Patient charts were selected for inclusion in this study if they carried a diagnosis of neovascular glaucoma and underwent Ahmed glaucoma valve implantation only, Ahmed glaucoma valve implantation with cyclophotocoagulation, or cyclophotocoagulation only. A total of 55 eyes of 54 patients were selected for data collection and analysis. Main outcome measures included 1-, 3-, and 6-month intraocular pressure and occurrence of the hypertensive phase. Other outcomes included visual acuity, surgical complication rate, and a number of 6-month postoperative ophthalmic medications. Results: A significantly lower intraocular pressure was seen in the group that received Ahmed glaucoma valve implantation + cyclophotocoagulation compared to the Ahmed glaucoma valve-only group at 3 and 6 months (p = 0.03 and <0.001, respectively). The difference in the occurrence of the hypertensive phase between the Ahmed glaucoma valve-only group and the Ahmed glaucoma valve + cyclophotocoagulation group approached but did not reach significance (p = 0.052). A significantly lower intraocular pressure was also seen in the cyclophotocoagulation-only group compared to the Ahmed glaucoma valve-only group at 3 months (p = 0.006). Conclusion: Simultaneous Ahmed glaucoma valve implantation and cyclophotocoagulation significantly lowered intraocular pressure at 3 and 6 months compared to Ahmed glaucoma valve implantation alone in patients with neovascular glaucoma. Clinical significance: Neovascular glaucoma is difficult to manage medically and surgically. When surgery is performed, intraocular pressure often remains elevated postoperatively despite aggressive medical management. This study examines a novel method to lower intraocular pressure after Ahmed glaucoma valve implantation in patients with neovascular glaucoma. How to cite this article: Ford RL, Knight ORJ, Klifto MR, et al. A Pilot Study Assessing Treatment Outcomes in Neovascular Glaucoma Using Ahmed Glaucoma Valve with and without Cyclophotocoagulation. J Curr Glaucoma Pract 2022;16(1):4-10.

Juvenile open angle glaucoma: current diagnosis and management.

PURPOSE OF REVIEW: The aim of this article is to summarize up-to-date research on the diagnosis and management of juvenile open-angle glaucoma (JOAG). RECENT FINDINGS: JOAG can be subclassified into four clinical phenotypes, and faster myopic shift is a risk factor for disease progression. Vessel density is associated with structural damage and worsening visual acuity in JOAG and can be monitored with optical coherence tomography angiography. Genetic studies have revealed molecular causes of JOAG including variants in CPAMD8, MYOC, and CYP1B1. Tube shunt surgeries as well as gonioscopy-assisted transluminal trabeculotomy have been shown to be successful in JOAG. SUMMARY: Although genetic advances may improve future screening, intraocular pressure monitoring and fundoscopic exam remain the current mainstay of diagnosis. Medical treatment alone for JOAG is typically insufficient with patients requiring surgical management. Selective laser trabeculoplasty may delay or decrease the need for surgery. Trabeculectomy has traditionally been shown to be effective in JOAG, but tube shunt surgery and microinvasive glaucoma surgery are effective alternatives.

Chronic Kidney Disease as a Predictor of Postoperative Choroidal Effusions After Glaucoma Surgery.

PRCIS: Patients with chronic kidney disease (CKD) are at increased risk for choroidal effusion development following glaucoma surgery. PURPOSE: Choroidal effusion is a postoperative complication of glaucoma surgery that results from a transudative fluid collection in the suprachoroidal space. Kidney disease alters bodily fluid dynamics through a variety of mechanisms. The relationship between CKD and choroidal effusion following glaucoma surgery has not previously been studied. The purpose of this study was to determine the relationship between CKD and choroidal effusion development after glaucoma surgery. PATIENTS AND METHODS: This retrospective cohort study consisted of 86 eyes from 86 patients who received glaucoma filtering surgery or transscleral cyclophotocoagulation within the study timeframe. Forty-three patients had CKD, and 43 patients did not have kidney disease. The main outcome of this study was the development of choroidal effusion measured by the Pearson χ2 test and multivariate analysis using a binomial regression with a log link. RESULTS: Ten patients (23.3%) in the CKD group developed choroidal effusion, while 2 patients (4.7%) in the no-kidney disease group developed choroidal effusion (relative risk, 5.0; 95% confidence interval: 1.16-21.5; P=0.013). The association between CKD and choroidal effusion showed mixed results in the multivariate analysis, with some analyses showing a significant association and others showing no significant association. CONCLUSIONS: In both the univariate and multivariate analyses, CKD was found to be significantly associated with choroidal effusion after glaucoma surgery.

Ahmed and Baerveldt Drainage Implants in the Treatment of Juvenile Open-angle Glaucoma.

PRECIS: Ahmed and Baerveldt implants succeed in 90.7% of cases for lowering intraocular pressure (IOP) <21 mm Hg at 1 year when used for the treatment of juvenile open-angle glaucoma. PURPOSE: The purpose of this study was to report the 1-year outcomes of Ahmed and Baerveldt tubes as the treatment for juvenile open-angle glaucoma at an academic institution. PATIENTS AND METHODS: Patients 18 to 40 years of age at the time of juvenile open-angle glaucoma diagnosis, who had inadequately controlled glaucoma with an IOP of 18 mm Hg or more on maximum tolerated antiglaucoma therapy that underwent tube shunt surgery with at least 6 months of follow-up were eligible for the study. Exclusion criteria included evidence of neovascular, uveitic or inflammatory, steroid-induced or primary congenital glaucoma, or if they did not have light perception vision. Postoperative failure was defined as an IOP, with or without antiglaucoma drops, >21 mm Hg for 2 consecutive visits after 3 months from surgery, <20% decrease in IOP at 1 year, no light perception, or revision of an implant due to high IOP. RESULTS: The study population included 32 eyes from 25 patients who underwent tube shunt surgery. The failure rate at 1-year follow-up was 9.3%, and the postoperative complication rate at 1-year follow-up was 9.3%. The average change from baseline to 1 year for IOP was a decrease of 9.8±9.10, for the number of antiglaucoma drops number was a decrease of 0.38±1.06, and for the visual acuity was an increase of 0.03±0.27. CONCLUSIONS: Ahmed and Baerveldt implantation succeeded in lower IOP in 90.7% of patients at 1 year. Continuation of antiglaucoma drops to maintain the IOP after surgery is likely required.

The Relationship of Travel Distance to Postoperative Follow-up Care on Glaucoma Surgery Outcomes.

PRéCIS:: This study addresses the paucity of literature examining glaucoma patients' distance from clinic on postoperative follow-up outcomes. Greater distance from clinic was associated with higher likelihood of loss to follow-up and missed appointments. PURPOSE: To investigate the relationship of patient travel distance and interstate access to glaucoma surgery postoperative follow-up visit attendance. METHODS AND PARTICIPANTS: Retrospective longitudinal chart review of all noninstitutionalized adult glaucoma patients with initial trabeculectomies or drainage device implantations between April 4, 2014 and December 31, 2018. Patients were stratified into groups on the basis of straight-line distance from residence to University of North Carolina at Chapel Hill's Kittner Eye Center and distance from residence to interstate access. Corrective procedures, visual acuity, appointment cancellations, no-shows, and insurance data were recorded. Means were compared using 2-tailed Student t-test, Pearson χ, analysis of variance, and multivariate logistical regression determined odds ratios for loss to follow-up. RESULTS: In total, 199 patients met all inclusion criteria. Six-month postoperatively, patients >50 miles from clinic had greater odds of loss to follow-up compared with patients <25 miles (odds ratios, 3.47; 95% confidence interval, 1.24-4.12; P<0.05). Patients >50 miles from clinic had significantly more missed appointments than patients 25 to 50 miles away, and patients <25 miles away (P=0.008). Patients >20 miles from interstate access had greater loss to follow-up than those <10 miles (t(150)=2.05; P<0.05). Mean distance from clinic was 12.59 miles farther for patients lost to follow-up (t(197)=3.29; P<0.01). Patients with Medicaid coverage had more missed appointments than those with Medicare plans (t(144)=-2.193; P<0.05). CONCLUSIONS: Increased distance from clinic and interstate access are associated with increased missed appointments and loss to follow-up. Glaucoma specialists should consider these factors when choosing surgical interventions requiring frequent postoperative evaluations.

pH of Mitomycin-C Formulations for Filtration Surgery.

PRECIS: The use of mitomycin-C as a mixed formulation with lidocaine and epinephrine for filtration surgery may alter its pH and consequently affect clinical effectivity.

BILATERAL COATS REACTION IN BANNAYAN-ZONANA SYNDROME: A SINGLE CASE REPORT.

PURPOSE: To report the clinical features of bilateral Coats reaction in a patient with Bannayan-Zonana syndrome. METHODS: The clinical course and retinal manifestations of a 21-year-old patient with Bannayan-Zonana syndrome and bilateral Coats reaction were studied. Retinal manifestations were documented with clinical examination, ultrawide-field color imaging, and ultrawide-field fluorescein angiography. RESULTS: Best-corrected visual acuities were 20/25 OD and 20/25 OS. Anterior segment examinations were normal bilaterally. The inferotemporal quadrant of the left retina demonstrated retinal telangiectasias, exudation, and a neurosensory retinal detachment extending to the mid-periphery. Fluorescein angiography demonstrated bilateral peripheral nonperfusion and vascular staining. An epiretinal membrane also involved the left macula. CONCLUSION: Bannayan-Zonana syndrome is an autosomal-dominant, hamartomatous disease characterized by a mutation spectrum that involves genes responsible for vascular development. Retinal vascular abnormalities and exudation can be a manifestation of this syndrome.

Fractal Dimensional Analysis of Optical Coherence Tomography Angiography in Eyes With Diabetic Retinopathy.

PURPOSE: We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). METHODS: A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. RESULTS: The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 × 10-3) and deep (P = 2.653 × 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 × 10-5) and deep (P = 3.120 × 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. CONCLUSIONS: The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.