Characterization of neural damage and neuroinflammation in Pax6 small-eye mice.

Aniridia is a panocular condition characterized by a partial or complete loss of the iris. It manifests various developmental deficits in both the anterior and posterior segments of the eye, leading to a progressive vision loss. The homeobox gene PAX6 plays an important role in ocular development and mutations of PAX6 have been the main causative factors for aniridia. In this study, we assessed how Pax6-haploinsufficiency affects retinal morphology and vision of Pax6Sey mice using in vivo and ex vivo metrics. We used mice of C57BL/6 and 129S1/Svlmj genetic backgrounds to examine the variable severity of symptoms as reflected in human aniridia patients. Elevated intraocular pressure (IOP) was observed in Pax6Sey mice starting from post-natal day 20 (P20). Correspondingly, visual acuity showed a steady age-dependent decline in Pax6Sey mice, though these phenotypes were less severe in the 129S1/Svlmj mice. Local retinal damage with layer disorganization was assessed at P30 and P80 in the Pax6Sey mice. Interestingly, we also observed a greater number of activated Iba1+ microglia and GFAP + astrocytes in the Pax6Sey mice than in littermate controls, suggesting a possible neuroinflammatory response to Pax6 deficiencies.

Global and Regional Damages in Retinal Ganglion Cell Axon Bundles Monitored Non-Invasively by Visible-Light Optical Coherence Tomography Fibergraphy.

Retinal ganglion cells (RGCs) exhibit compartmentalized organization, receiving synaptic inputs through their dendrites and transmitting visual information from the retina to the brain through the optic nerve. Little is known about the structure of RGC axon bundles extending from individual RGC somas to the optic nerve head (ONH) and how they respond to disease insults. We recently introduced visible-light optical coherence tomography fibergraphy (vis-OCTF), a technique for directly visualizing and analyzing mouse RGC axon bundles in vivo In this study, we validated vis-OCTF's ability to quantify RGC axon bundles with an increased number of RGCs using mice deficient in BCL2-associated X protein (BAX-/-). Next, we performed optic nerve crush (ONC) injury on wild-type (WT) mice and showed that the changes in RGC axon bundle width and thickness were location-dependent. Our work demonstrates the potential of vis-OCTF to longitudinally quantify and track RGC damage at single axon bundle level in optic neuropathies.SIGNIFICANCE STATEMENT Nearly all clinical and preclinical studies measure the retinal nerve fiber (RNFL) thickness as the sole indicator of retinal ganglion cell (RGC) damage without investigating RGC axon bundles directly. We demonstrated visible-light optical coherence tomography fibergraphy (vis-OCTF) to directly quantify global and regional RGC axon bundle organizations in vivo as a new biomarker for RGC health. We validated in vivo vis-OCTF measures using both confocal microscopy of the immunostained flat-mounted retina and numerical simulations. Vis-OCTF for monitoring RGC axon bundle organization has the potential to bring new insight into RGC damage in optic neuropathies.

In vivo imaging of the inner retinal layer structure in mice after eye-opening using visible-light optical coherence tomography.

The growth of the mouse eye and retina after birth is a dynamic, highly regulated process. In this study, we applied visible-light optical coherence tomography (vis-OCT), a non-invasive imaging technique, to examine developing retinal layer structures after eye-opening. We introduced a resampled circumpapillary B-scan averaging technique to improve the inter-layer contrast, enabling retinal layer thickness measurements as early as postnatal day 13 (P13) - right after eye-opening. We confirmed vis-OCT measurements using ex vivo confocal microscopy of retinal sections at different ages. Our results demonstrate that vis-OCT can visualize the developmental murine retinal layer structure in vivo, which offers us new opportunities to better characterize the pathological alterations in mouse models of developmental eye diseases.

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients.

Mutations in the Pax6 gene cause ocular defects in both vertebrate and invertebrate animal species, and the disease aniridia in humans. Despite extensive experimentation on this gene in multiple species, including humans, we still do not understand the earliest effects on development mediated by this gene. This prompted us to develop pax6 mutant lines in Xenopus tropicalis taking advantage of the utility of the Xenopus system for examining early development and in addition to establish a model for studying the human disease aniridia in an accessible lower vertebrate. We have generated mutants in pax6 by using Transcription Activator-Like Effector Nuclease (TALEN) constructs for gene editing in X. tropicalis. Embryos with putative null mutations show severe eye abnormalities and changes in brain development, as assessed by changes in morphology and gene expression. One gene that we found is downregulated very early in development in these pax6 mutants is myc, a gene involved in pluripotency and progenitor cell maintenance and likely a mediator of some key pax6 functions in the embryo. Changes in gene expression in the developing brain and pancreas reflect other important functions of pax6 during development. In mutations with partial loss of pax6 function eye development is initially relatively normal but froglets show an underdeveloped iris, similar to the classic phenotype (aniridia) seen in human patients with PAX6 mutations. Other eye abnormalities observed in these froglets, including cataracts and corneal defects, are also common in human aniridia. The frog model thus allows us to examine the earliest deficits in eye formation as a result of pax6 lesions, and provides a useful model for understanding the developmental basis for the aniridia phenotype seen in humans.

Visible-Light Optical Coherence Tomography Fibergraphy of the Tree Shrew Retinal Ganglion Cell Axon Bundles.

We seek to develop techniques for high-resolution imaging of the tree shrew retina for visualizing and parameterizing retinal ganglion cell (RGC) axon bundles in vivo. We applied visible-light optical coherence tomography fibergraphy (vis-OCTF) and temporal speckle averaging (TSA) to visualize individual RGC axon bundles in the tree shrew retina. For the first time, we quantified individual RGC bundle width, height, and cross-sectional area and applied vis-OCT angiography (vis-OCTA) to visualize the retinal microvasculature in tree shrews. Throughout the retina, as the distance from the optic nerve head (ONH) increased from 0.5 mm to 2.5 mm, bundle width increased by 30%, height decreased by 67%, and cross-sectional area decreased by 36%. We also showed that axon bundles become vertically elongated as they converge toward the ONH. Ex vivo confocal microscopy of retinal flat-mounts immunostained with Tuj1 confirmed our in vivo vis-OCTF findings.

Comparative In Vivo Imaging of Retinal Structures in Tree Shrews, Humans, and Mice.

Rodent models, such as mice and rats, are commonly used to examine retinal ganglion cell damage in eye diseases. However, as nocturnal animals, rodent retinal structures differ from primates, imposing significant limitations in studying retinal pathology. Tree shrews (Tupaia belangeri) are small, diurnal paraprimates that exhibit superior visual acuity and color vision compared with mice. Like humans, tree shrews have a dense retinal nerve fiber layer (RNFL) and a thick ganglion cell layer (GCL), making them a valuable model for investigating optic neuropathies. In this study, we applied high-resolution visible-light optical coherence tomography to characterize the tree shrew retinal structure in vivo and compare it with that of humans and mice. We quantitatively characterize the tree shrew's retinal layer structure in vivo, specifically examining the sublayer structures within the inner plexiform layer (IPL) for the first time. Next, we conducted a comparative analysis of retinal layer structures among tree shrews, mice, and humans. We then validated our in vivo findings in the tree shrew inner retina using ex vivo confocal microscopy. The in vivo and ex vivo analyses of the shrew retina build the foundation for future work to accurately track and quantify the retinal structural changes in the IPL, GCL, and RNFL during the development and progression of human optic diseases.

Screening for glaucoma: rationale and strategies.

PURPOSE OF REVIEW: Late diagnosis of glaucoma is a leading factor in vision loss associated with this disease. Screening programs seek to diagnose glaucoma at an earlier, more treatable stage. Our purpose was to review the influence of screening location and testing strategies in glaucoma screening. RECENT FINDINGS: Screening high-risk groups appears effective, although general population-based screening programs have not been cost effective. Community-based screening programs have achieved limited success due to lack of follow-up of screened patients. High-risk patients often do not present for office-based screening programs. Screening strategies that employ a single test or few tests are generally more effective compared with strategies using multiple tests, due to avoidance of false positives. Compared with currently available screening tests, frequency-doubling technology (FDT) perimetry has shown higher sensitivity and specificity. Recent evidence suggests that automated assessment of the optic nerve and retinal nerve fiber layer may be superior to FDT perimetry, but the techniques remain unproven in screening settings. SUMMARY: Community-based screening of high-risk groups with functional testing using FDT perimetry can be effective, but newer automated structural measurements of the optic nerve and retinal nerve fiber layer may allow improved glaucoma screening sensitivity and specificity in the future.

Visual Acuity in Aniridia and WAGR Syndrome.

Purpose: Our purpose was to evaluate visual acuity in aniridia subjects and the more severely affected phenotype in WAGR syndrome subjects, and to assess potential impact on visual function. Materials and Methods: This was a retrospective comparative study of 25 aniridia subjects with nonsense mutations of PAX6 (50 eyes) and 25 WAGR syndrome subjects with large deletion mutations involving PAX6 (50 eyes). Aniridia subjects were age- and gender-matched with WAGR syndrome subjects in the Coordination of Rare Diseases at Sanford (CoRDS) database. Best-corrected ETDRS visual acuity measurements were converted to LogMAR visual acuity values, which were used to perform statistical analyses. Results: The age and gender distribution of the subjects was not statistically significantly different. The mean LogMAR values in aniridia and WAGR syndrome subjects were 0.95±0.53 and 1.51±0.99, respectively (P<0.001). In the better-seeing eye, mean LogMAR values were 0.78±0.15 in aniridia subjects and 1.40±0.88 in WAGR syndrome subjects (P=0.001). The mean LogMAR values for the better-seeing eye corresponded to Snellen visual acuity of 20/125 in aniridia subjects and 20/500 in WAGR syndrome subjects. This average visual acuity was worse than the threshold for profound visual impairment (WHO criteria) and legal blindness (AAO criteria) in WAGR syndrome but not in aniridia subjects. In analysis of both eyes, the visual efficiency was 34% in aniridia subjects and 2% in WAGR syndrome subjects. Conclusion: Visual acuity was significantly worse in WAGR subjects with multi-gene deletion mutations compared with aniridia subjects with nonsense mutations, which corresponded to differences in standard visual function thresholds. Our results suggest that visual acuity may indicate severity of ocular involvement and variability of phenotype in aniridia and WAGR syndrome.

Report on the 2021 Aniridia North America symposium on PAX6, aniridia, and beyond.

The inaugural Aniridia North America (ANA) Symposium was held on the first weekend in November 2021 in Charlottesville, VA, at the University of Virginia. The purpose of this meeting was to bring together an international group of scientists, physicians, patient advocacy groups, and individuals with aniridia to discuss recent advances in knowledge about aniridia and other congenital eye diseases and the development of potential treatments for congenital eye disorders using personalized medicine. Leaders in several areas of eye research and clinical treatment provided a broad perspective on new research advances that impact an understanding of the causes of the damage to the eye associated with aniridia and the development of novel treatments for this and related disorders. Here we summarize the research discussed at the symposium.

Longitudinal Analysis of Retinal Ganglion Cell Damage at Individual Axon Bundle Level in Mice Using Visible-Light Optical Coherence Tomography Fibergraphy.

Purpose: We developed a new analytic tool based on visible-light optical coherence tomography fibergraphy (vis-OCTF) to longitudinally track individual axon bundle transformation as a new in vivo biomarker for retinal ganglion cell (RGC) damage. Methods: After acute optic nerve crush injury (ONC) in mice, we analyzed four parameters: lateral bundle width, axial bundle height, cross-sectional area, and the shape of individual bundles. We next correlated the morphological changes in RGC axon bundles with RGC soma loss. Results: We showed that axon bundles became wider and taller at three days post ONC (pONC), which correlated with about 15% RGC soma loss. At six days pONC, axon bundles showed a significant reduction in lateral width and cross-sectional area, followed by a reduction in bundle height at nine days pONC. Bundle shrinking at nine days pONC correlated with about 68% RGC soma loss. Both experimental and simulated results suggested that the cross-sectional area of individual RGC axon bundles is more sensitive than bundle width and height to indicate RGC soma loss. Conclusions: This study is the first to track and quantify individual RGC axon bundles in vivo after ONC injury. Translational Relevance: Recognizing RGC loss at its earliest stage is crucial for disease diagnosis and treatment. However, current clinical methods to detect the functional and structural changes in the inner retina are not sensitive enough to directly assess RGC health. In this study, we developed vis-OCTF-based parameters to track RGC damage, making possible to establishing a quantifiable biomarker for glaucoma.

Visible-Light Optical Coherence Tomography Fibergraphy of the Tree Shrew Retinal Ganglion Cell Axon Bundles.

We seek to develop techniques for high-resolution imaging of the tree shrew retina for visualizing and parameterizing retinal ganglion cell (RGC) axon bundles in vivo. We applied visible-light optical coherence tomography fibergraphy (vis-OCTF) and temporal speckle averaging (TSA) to visualize individual RGC axon bundles in the tree shrew retina. For the first time, we quantified individual RGC bundle width, height, and cross-sectional area and applied vis-OCT angiography (vis-OCTA) to visualize the retinal microvasculature in tree shrews. Throughout the retina, as the distance from the optic nerve head (ONH) increased from 0.5 mm to 2.5 mm, bundle width increased by 30%, height decreased by 67%, and cross-sectional area decreased by 36%. We also showed that axon bundles become vertically elongated as they converge toward the ONH. Ex vivo confocal microscopy of retinal flat-mounts immunostained with Tuj1 confirmed our in vivo vis-OCTF findings.

Stand-Alone Xen Gel Microstent Implantation Compared With Kahook Dual Blade Goniotomy.

PRCIS: Both Xen gel Microstent implantation and Kahook Dual Blade (KDB) goniotomy are safe and effective as stand-alone procedures, but the Xen Gel Microstent was associated with more postoperative interventions and achieved higher success at a lower intraocular pressure threshold. PURPOSE: To evaluate outcomes of stand-alone Xen Gel Microstent implantation compared with stand-alone KDB goniotomy for moderate to severe glaucoma. METHODS: A retrospective, single-center, case-series analysis comparing outcomes of Xen Gel Microstent implantation and KDB goniotomy stand-alone cases in 75 eyes. Primary outcomes included intraocular pressure (IOP) reduction, glaucoma medication reduction, surgical success, and complications. Surgical success was defined using IOP<21 mm Hg and IOP<18 mm Hg thresholds, with or without glaucoma medications, and without further glaucoma surgery. Subjects were followed for at least 24 months after surgery. RESULTS: Mean baseline IOP was comparable between the Xen Gel Microstent and KDB goniotomy groups (23.7±8.4 and 25.9±7.9 mm Hg, respectively, P =0.32). At 24 months after surgery, the mean IOP after Xen Gel Microstent was 14.7±3.2 mm Hg (32.7% reduction from baseline, P =0.018) and KDB goniotomy was 16.7±3.2 mm Hg (40.4% reduction from baseline, P =0.049). Although the mean IOP was significantly lower during the first month after Xen Gel Microstent implantation, no difference in mean IOP was observed between the 2 treatment groups at 24 months after surgery ( P =0.416). At 24 months after surgery, the percent reduction of IOP from baseline was not significantly different between the 2 groups. The mean reduction of glaucoma medications from baseline at 24 months was 1.69 drops after Xen Gel Microstent implantation ( P =.008) and 1.67 drops after KDB goniotomy ( P =0.038). Postoperative complications were nonvision-threatening and were not significantly different between the 2 groups ( P =0.550). Interventions not included with complications were needling performed in 21 (37%) of eyes in the Xen Gel Microstent group and Nd:YAG goniopuncture in 1 (5.6%) eye after KDB goniotomy. With an IOP threshold <21 mm Hg, surgical success was not significantly different between the 2 groups ( P =0.06). At a lower IOP threshold (<18 mm Hg), surgical success was higher after Xen Gel Microstent implantation compared with KDB goniotomy ( P =0.001). CONCLUSIONS: Both stand-alone Xen Gel Microstent implantation and KDB goniotomy can effectively and safely reduce IOP for moderate to severe glaucoma. The Xen Gel Microstent was associated with a higher need for postoperative interventions and achieved greater success at a lower IOP threshold.

CNS targets support and sustain differentiation of cultured neuronal and retinal progenitor cells.

Superior colliculus (SC) is the target of retinal neurons, allowing them to form connections. Cultured stem cells/progenitors can potentially be used as donor tissue to reconstruct degenerated retina including perhaps replacing lost ganglion cells in glaucoma. In which case, it will be essential for these cells to integrate with the central nervous system targets. Here, we have investigated if the mid-brain region containing superior colliculus (SC) provides a permissive environment for the survival and differentiation of neural progenitors, including retinal progenitor cells propagated in cultures. Neural (NPCs) and retinal progenitor cells (RPCs) from green fluorescent protein (GFP) transgenic mice were cultured. Passage two through four neural and retinal progenitor cells were subsequently cocultured with the SC organotypic slices and maintained in culture for 17 and eight days respectively. Differentiation of the neurons was studied by immunocytochemistry for retinotypic neuronal markers. Retinal progenitor cells cocultured with SC slices were able to differentiate into various neuronal morphologies. Some cocultured progenitor cells differentiated into neurons as suggested by class III ß tubulin immunoreactivity. In addition, specific retinotypic neuronal differentiation of RPC was detected by immunoreactivity for calbindin and PKC. SC provides a permissive environment that supports survival and differentiation of the progenitor cells.

Influence of pupil size and other test variables on visual function assessment using visual evoked potentials in normal subjects.

The purpose of this study was to assess the influence of pupil size and optical blur on measurements obtained with isolated-check visual evoked potential (icVEP). Two stimulus conditions of icVEP, +15 and -15% contrasts, were studied in normal subjects with normal (N), miotic (M), and dilated (D) pupils. The effects of optical blur were studied in subjects with normal pupil. Response to visual stimuli was quantified by a signal-to-noise (SNR) ratio. In 30 normal subjects, the mean age was 26.0 +/- 3.4 years. Mean pupil diameters were N = 4.2 +/- 0.6 mm, M = 2.7 +/- 0.6 mm, and D = 7.3 +/- 0.9 mm. For both +15 and -15% contrast levels, mean SNR values were reduced for dilated and constricted pupils when compared with normal pupils. Mean SNR values for optical blur with a +2 or +3 diopter lens placed over the distance correction were reduced when compared with SNR measurements obtained with best-corrected visual acuity under both +15 and -15% contrast levels. Statistical significance was found in comparisons of N versus M (P < 0.001) and N versus D (P = 0.002) for +15 and -15% contrast conditions, respectively. No statistical difference was seen for M versus D (P = -0.435). The effect of optical blur was statistically significant when compared to the normal pupils with best-corrected vision (P < 0.001). No statistically significant difference was found comparing +2 and +3 diopters lenses for optical blur testing. Visual evoked potential values are influenced by pupillary constriction and dilation, as well as optical blur. When obtaining icVEP measurements, the influence of pupil size and optical blur should be kept in mind for accurate interpretations.

Treatment of Uveitis and Outcomes of Glaucoma Drainage Implant Surgery: A Meta-Analysis.

PURPOSE: We performed a meta-analysis to evaluate the effect of uveitis treatment on glaucoma drainage implant surgical outcomes. METHODS: We included 16 articles in the meta-analysis. Two groups were defined based on medical therapy of uveitis: Group 1: poorly controlled uveitis, and Group 2: well-controlled uveitis including use of immunomodulatory medications. RESULTS: The two groups were similar in comparisons of follow-up time, age, gender, and etiology of uveitis. Meta-analysis demonstrated significantly greater success in Group 2 (95.1%) compared to Group 1 (81.6%) at 1 year after glaucoma drainage implant surgery (P = .001). The final success was significantly greater (P 0.014) in group 2 compared with group 1 (86.1% and 74.3%, respectively). CONCLUSION: Surgical success was significantly higher in uveitic glaucoma patients treated with more intensive immunosuppressive therapy before and after glaucoma drainage implant surgery. The level of control of uveitis perioperatively appears to influence glaucoma drainage implant surgery outcomes.

Visible-Light Optical Coherence Tomography Fibergraphy for Quantitative Imaging of Retinal Ganglion Cell Axon Bundles.

Purpose: To develop a practical technique for visualizing and quantifying retinal ganglion cell (RGC) axon bundles in vivo. Methods: We applied visible-light optical coherence tomography (vis-OCT) to image the RGC axon bundles, referred to as vis-OCT fibergraphy, of healthy wild-type C57BL/6 mice. After vis-OCT imaging, retinas were flat-mounted, immunostained with anti-beta-III tubulin (Tuj1) antibody for RGC axons, and imaged with confocal microscopy. We quantitatively compared the RGC axon bundle networks imaged by in vivo vis-OCT and ex vivo confocal microscopy using semi-log Sholl analysis. Results: Side-by-side comparison of ex vivo confocal microscopy and in vivo vis-OCT confirmed that vis-OCT fibergraphy captures true RGC axon bundle networks. The semi-log Sholl regression coefficients extracted from vis-OCT fibergrams (3.7 ± 0.8 mm-1) and confocal microscopy (3.6 ± 0.3 mm-1) images also showed good agreement with each other (n = 6). Conclusions: We demonstrated the feasibility of using vis-OCT fibergraphy to visualize RGC axon bundles. Further applying Sholl analysis has the potential to identify biomarkers for non-invasively assessing RGC health. Translational Relevance: Our novel technique for visualizing and quantifying RGC axon bundles in vivo provides a potential measurement tool for diagnosing and tracking the progression of optic neuropathies.

Comparison of Silicone- and Porous-Plate Ahmed Glaucoma Valves.

PURPOSE: Our aim was to evaluate and compare the clinical outcomes after implantation of the silicone-plate (model FP7) and porous polyethylene-plate (model M4) Ahmed Glaucoma Valves. PATIENTS AND METHODS: This was a prospective, multicenter, comparative series. A total of 52 eyes (52 patients) were treated with either the silicone or porous plate Ahmed Glaucoma Valve implant. Hypertensive phase was defined as intraocular pressure >21 mmHg during the first 3 months postoperatively. Success was defined as 5 mmHg ≤intraocular pressure ≤21 mmHg (with or without additional glaucoma medications), without loss of light perception and without additional glaucoma procedures. Patients were monitored for 1 year after surgery. RESULTS: The pre-operative intraocular pressure was 29.9 ± 6.6 mmHg and 33.8 ± 10.5 in the silicone-plate and porous-plate groups, respectively (P = 0.118). At 12 months after surgery, the mean intraocular pressure was 13.6 ± 4.7 mmHg in the silicone-plate group and 17.9 ± 10.9 mmHg in the porous-plate group (P = 0.141). The mean number of glaucoma medications at 12 months was 1.64 ± 1.40 mmHg and 1.89 ± 1.54 mmHg in the silicone- and porous-plate groups, respectively (P = 0.605). Hypertensive phase was not significantly different in the two groups (50.0% of the silicone-plate and 57.7% of the porous-plate groups, P = 0.578). At 12 months after surgery, the percent success for the silicone-plate and porous-plate groups was 88.5% and 53.8%, respectively (P = 0.005). Complications were similar in the two groups. CONCLUSION: The porous-plate Ahmed Glaucoma Valve showed similar average intraocular pressure reduction compared with the silicone-plate model. At 12 months after surgery, there was a significantly lower success rate in the porous-plate compared with the silicone-plate group.

A clinical approach for evaluation of glaucoma patients.

Clinicians are confronted with a plethora of new machines, new software, and new applications of technology, all intended to help with glaucoma management. It is helpful to return to basic principles, to see how these advances fit into our assessment of the intraocular pressure, optic nerve, and visual fields.

Anterior chamber angle in aniridia with and without glaucoma.

PURPOSE: We performed a retrospective, comparative study to determine if patients with aniridia and glaucoma had open angles on high-resolution anterior segment optical coherence tomography (OCT) and clinical gonioscopy. PATIENTS AND METHODS: Forty-three patients (86 eyes) with aniridia had recorded anterior segment OCTs, gonioscopy, or both. Of these patients, 27 (54 eyes) were diagnosed with glaucoma and 16 (32 eyes) had no evidence of glaucoma. All patients had either anterior segment OCT, gonioscopy, or both. RESULTS: The 43 patients with aniridia had average age of 32±17 years, and 27 (62%) were female. Anterior segment OCT and gonioscopy were recorded in 25 (58%) of the patients and 18 (42%) of the patients had gonioscopy alone. Of the 54 eyes with aniridia and glaucoma, 4 (7%) eyes in 3 patients (11%) had partial or completely closed angles. Of the 32 eyes without glaucoma, all (100%) had open angles. The proportion of open angles in the aniridia with glaucoma eyes was not significantly different compared with the aniridia without glaucoma eyes (P=0.32). Of the 4 eyes with closed angles, all had a history of prior surgery for cataract, glaucoma, and/or keratopathy. The proportion of eyes with prior surgery was significantly higher in eyes with open-angle glaucoma and angle-closure glaucoma compared with eyes without glaucoma (P<0.001 and P=0.002, respectively). CONCLUSION: The majority of eyes with aniridia and glaucoma have open anterior chamber angles, similar to patients with aniridia without glaucoma. All eyes with aniridia and glaucoma that had closed angles had a prior history of ocular surgery.

Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes.

PRéCIS:: Intravitreal anti-vascular endothelial growth factor (VEGF) injections may accelerate glaucomatous change in patients with preexisting glaucoma or ocular hypertension (OHT). The safety of long-term injections in this specific population may be reflected in the need for additional glaucoma interventions. PURPOSE: The purpose of this study was to investigate whether repeated anti-VEGF injections accelerate structural and functional glaucomatous change in eyes with preexisting glaucoma or OHT. MATERIALS AND METHODS: This is a retrospective, observational study of injected and noninjected fellow eyes. A total of 28 patients with preexisting glaucoma or OHT, who received ≥6 unilateral anti-VEGF injections for concurrent neovascular retinal disease, were selected for chart review. Primary outcome measures were rate of visual field loss in dB/year, rate of change in retinal nerve fiber layer (RNFL) thickness in microns/year, and need for additional glaucoma medications, surgery, or laser. RESULTS: The number of eyes requiring additional glaucoma surgery or laser was 8 of 28 (28.6%) for the injected group and 2 of 28 (7.1%) for the noninjected group. A significantly greater proportion of injected eyes required invasive glaucoma intervention (P=0.034). Average rate of decline in mean deviation and change in pattern standard deviation were both significantly greater in injected eyes (P=0.029; P=0.019). Estimated mean rate of global retinal nerve fiber layer change was -4.27 µm/y for the injected group and -1.17 µm/y for the noninjected group and was significant only for injected eyes (P=0.014). Only the superior quadrant exhibited thinning that was significantly different between groups (P=0.030). CONCLUSIONS: Intravitreal injections were associated with accelerated functional and structural glaucoma-like change in susceptible eyes. Clinicians should assess the need for glaucoma medications or other interventions over the course of anti-VEGF therapy.