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PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.

PURPOSE: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. METHODS: Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing additional glaucoma surgery, or the inability to maintain ≥ 20% IOP reduction from baseline with IOP between 5-18 mmHg while maintaining ≤ baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. RESULTS: Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 ± 4.7 mmHg phaco/ECP, 18.37 ± 4.6 mmHg phaco/MP-TSCPC, 14.30 ± 4.2 mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1 year between groups. Mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. There were no differences in complication rates among the three groups. CONCLUSIONS: Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles.

PURPOSE: To describe the indications, outcomes, and complications associated with intraocular lens (IOL) exchange. PATIENTS AND METHODS: To determine the relative frequency of postoperative complications between techniques for all patients undergoing IOL exchange from May 1, 2014 through August 31, 2020. RESULTS: IOL exchange was performed in 511 eyes of 489 patients (59.7% men; mean age: 67.0 ± 13.9 years, median time from cataract procedure to IOL exchange: 47.5 months). Mean uncorrected visual acuity significantly improved from 20/192 Snellen equivalent (logMAR 0.981) preoperatively to 20/61 (logMAR 0.487) at last follow-up (P < 0.001). Overall, 384 eyes (78.7%) met their desired refractive outcome within ±1.0 diopter (D). The most frequent complication was cystoid macular edema (CME) (n=39, 7.6%). Iris-sutured technique was associated with significantly greater frequency of subsequent IOL dislocation (10.3%) than 4-point scleral sutured (0%, P = 0.002), anterior chamber IOL (ACIOL, 1.5%, P = 0.01), and 2-point scleral sutured (0%, P = 0.03) techniques. Yamane scleral-fixation technique was associated with significantly greater frequency of developing IOL tilt (11.8%) than ACIOL (0%, P = 0.002), 4-point scleral sutured (1.1%, P = 0.01), 2-point scleral sutured (0%, P = 0.04), and iris-sutured (0%, P = 0.04) techniques. CONCLUSION: IOL exchange significantly improved uncorrected visual acuity and more than three-quarters of eyes met the refractive goal. Certain techniques were associated with complications, including subsequent dislocation associated with iris-sutured technique and IOL tilt associated with Yamane scleral-fixation technique. This information may help guide surgeons in deciding between procedural techniques for individual patients during IOL exchange preoperative planning.

Astrocytes in the lamina region of the optic nerve head play vital roles in supporting retinal ganglion cell axon health. In glaucoma, these astrocytes are implicated as early responders to stressors, undergoing characteristic changes in cell function as well as cell morphology. Much of what is currently known about individual lamina astrocyte morphology has been learned from rodent models which lack a defining feature of the human optic nerve head, the collagenous lamina cribrosa (LC). Current methods available for evaluation of collagenous LC astrocyte morphology have significant shortcomings. We aimed to evaluate Multicolor DiOlistic labeling (MuDi) as an approach to reveal individual astrocyte morphologies across the collagenous LC. Gold microcarriers were coated with all combinations of three fluorescent cell membrane dyes, DiI, DiD, and DiO, for a total of seven dye combinations. Microcarriers were delivered to 150 μm-thick coronal vibratome slices through the LC of pig, sheep, goat, and monkey eyes via MuDi. Labeled tissues were imaged with confocal and second harmonic generation microscopy to visualize dyed cells and LC collagenous beams, respectively. GFAP labeling of DiOlistically-labeled cells with astrocyte morphologies was used to investigate cell identity. 3D models of astrocytes were created from confocal image stacks for quantification of morphological features. DiOlistic labeling revealed fine details of LC astrocyte morphologies including somas, primary branches, higher-order branches, and end-feet. Labeled cells with astrocyte morphologies were GFAP+. Astrocytes were visible across seven distinct color channels, allowing high labeling density while still distinguishing individual cells from their neighbors. MuDi was capable of revealing tens to hundreds of collagenous LC astrocytes, in situ, with a single application. 3D astrocyte models allowed automated quantification of morphological features including branch number, length, thickness, hierarchy, and straightness as well as Sholl analysis. MuDi labeling provides an opportunity to investigate morphologies of collagenous LC astrocytes, providing both qualitative and quantitative detail, in healthy tissues. This approach may open doors for research of glaucoma, where astrocyte morphological alterations are thought to coincide with key functional changes related to disease progression.

We aim to assess if genotype-phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort. We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children's Hospital and Cincinnati Children's Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C-terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow-up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk-stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.

The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis.

BACKGROUND: Recovery from amblyopia in adulthood after fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies, and the rate of recovery after FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine the frequency and degree of improvement in amblyopic eye (AE) visual function after ION in the FE. METHODS: We performed a retrospective chart review of patients between 2007 and 2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared the best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time. RESULTS: Among the 12 patients who met the inclusion criteria (mean age 67 ± 8 years), 9 (75%) improved ≥1 line and 2 (17%) improved ≥3 lines. The median time from ION symptom onset to maximal improvement was 6 months (range: 2-101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the AE for all patients, with mean improvement of 1.9 ± 1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE. CONCLUSIONS: A high proportion of patients with amblyopia and contralateral ION experience improvement in AEVA. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.

Mobile phone distraction is a significant contributor to pedestrian injuries. However, mobile phone engagement among pedestrians has been scarcely explored in a developing country like India. The present study utilized the beliefs-based theory of planned behaviour to examine the association between pedestrian beliefs towards distracted walking (behavioural, normative, and control) and their mobile phone use frequencies. Based on a survey of 560 pedestrians (64.6% males), it was found that the major use of mobile phones was for listening to music (30.7%), followed by receiving a call (25%), making a call (18.9%), texting (9.8%), navigation (8.5%) and internet browsing (7.1%). A series of multivariate ANOVAs and logistic regression models were developed to investigate the relationships between the beliefs and frequencies of mobile phone use in hands-free and hand-held conditions. Significant multivariate differences were found for behavioural and normative beliefs in hands-free conditions and all three types of beliefs in hand-held conditions. The frequency of mobile phone use was significantly predicted by normative beliefs (p < 0.001) in the hands-free condition, and by behavioural (p = 0.041) and normative beliefs (p = 0.004) in the hand-held condition. The findings may assist the road safety countermeasures in addressing the issue of pedestrian distraction.

PURPOSE: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). METHODS: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. RESULTS: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. CONCLUSIONS: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

INTRODUCTION: Currently, little is known regarding bone health surveillance for glucocorticoid-exposed non-infectious uveitis (NIU) patients or their baseline risks of skeletal fragility outcomes. METHODS: Using claims data, we calculated rates of dual-energy x-ray absorptiometry (DXA) screening for glucocorticoid-exposed NIU and rheumatoid arthritis (RA) patients. Separately, we compared risks of skeletal fragility metrics amongst NIU patients, RA patients, and controls, independent of glucocorticoid use. RESULTS: The adjusted hazard ratio (aHR) of NIU patients to have a DXA scan was 0.64 (95% CI, 0.63-0.65; p < .001) compared to RA patients. The aHR for any skeletal fragility outcome amongst NIU patients was 0.97 (p < .02) compared to normal controls, while RA patients had excess risk (aHR, 1.15; p < .001). CONCLUSIONS: NIU patients are 36% less likely to receive a DXA scan after high-dose glucocorticoid exposure compared with RA patients. No elevated risk of osteoporosis for NIU patients was found compared to normal controls.

PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95% CI, 1.6-1.8), and South (OR, 1.4; 95% CI, 1.3-1.5) and West (OR, 1.3; 95% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA < 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95% CI, 8.0-15.7), older age (e.g., > 80 years vs. < 21 years; OR, 5.8; 95% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

BACKGROUND: Neuro-ophthalmologists have expertise in rare and complex disorders, but the ability of patients to access neuro-ophthalmic care has not been examined at a nationwide level. METHODS: Using the 2020 directory of all 502 members of the North American Neuro-Ophthalmology Society as a reference, we found the practice locations of 461 confirmed practicing members and converted each street address to latitude and longitude coordinates. We calculated the travel distance and time from each census tract to the nearest practice location and calculated population-weighted averages by state, region, and other prespecified factors. Choropleth maps were used to visualize the distribution of travel distances and times across the United States. RESULTS: California had the most practicing neuro-ophthalmologists out of any state (50), whereas 4 states (DE, MT, SD, and WY) had none. Washington, DC and MA had the most neuro-ophthalmologists per capita. The average travel distance and time to the nearest neuro-ophthalmologists were found to be 40.90 miles and 46.50 minutes, respectively, although a large portion of western plains and mountain regions had travel times of over 120 minutes. Patients in rural areas had longer travel times than those in urban areas, and Native American patients had the longest travel times of any racial or ethnic group. CONCLUSION: The travel time to see a neuro-ophthalmologist varies widely by state, region, and rurality, with Native American patients and rural patients being disproportionately affected. By identifying the areas with the greatest travel burdens, future policies can work to alleviate these potential barriers to care.

OBJECTIVE: The head and intraocular trauma tool (HITT) is a portable, binocular retinal polarization scanner (RPS) that detects ocular fixation with high precision to assess visuomotor function. We conducted a pilot evaluation of a prototype binocular RPS device to evaluate alterations in fixation stability, binocularity (convergence), and saccadic latency after mild traumatic brain injury (mTBI). METHODS: Two groups were studied prospectively: (1) single observation study of mTBI patients in a hospital ER (n = 7) and age-matched controls (n = 43); (2) high-school athletes preseason (n = 28), after sports-related mTBI (n = 3), and at season end (n = 5). Subjects were asked to fixate on an internal target and track randomly presented peripheral and central targets as fixation was assessed using binocular RPS. RESULTS: There were clinically and statistically significant alterations in the hospital ER group after mTBI, including a decrease in fixation stability (54.6% in patents vs 90.2% in controls, p = 0.014) and binocularity (28.7% in patients vs 86.6% in controls; p = 0.004). Similar trends, not statistically significant, were observed in saccadic latency in the hospital ER group as well as in the injured high school athletes. CONCLUSION: The HITT device shows promise as an objective, noninvasive method for assessment of the impact of mTBI on visuomotor function. Additional studies with larger patient populations are required to evaluate efficacy for clinical use.

Discovering the secrets of diseases from tear extracellular vesicles (EVs) is well-recognized and appreciated. However, a precise understanding of the interaction network between EV populations and their biogenesis from our body requires more in-depth and systematic analysis. Here, we report the biological profiles of different-size tear EV subsets from healthy individuals and the origins of EV proteins. We have identified about 1800 proteins and revealed the preferential differences in the biogenesis among distinct subsets. We observe that eye-related proteins that maintain retinal homeostasis and regulate inflammation are preferentially enriched in medium-size EVs (100 to 200 nm) fractions. Using universal analysis in combination with the Human Protein Atlas consensus dataset, we found the genesis of tear EV proteins with 37 tissues and 79 cell types. The proteins related to retinal neuronal cells, glial cells, and blood and immune cells are selectively enriched among EV subsets. Our studies in heterogeneous tear EVs provide building blocks for future transformative precision molecular diagnostics and therapeutics.