Interim Analysis of Clinical Outcomes with Open versus Closed Conjunctival Implantation of the XEN45 Gel Stent.

OBJECTIVE: To examine the longitudinal postoperative outcomes of open versus closed conjunctiva implantation of the XEN45 gel stent. DESIGN: Retrospective multicenter study. SUBJECTS: One hundred ninety-three patients with glaucoma underwent XEN45 implantation via an open or closed conjunctiva approach. METHODS: Data on patient demographics; diagnoses; preoperative and postoperative clinical data; outcome measures, including intraocular pressure (IOP); use of glaucoma medications; visual acuity; and complications were collected. Statistical analyses were performed with P < 0.05 as significant. MAIN OUTCOME MEASURES: Failure was defined as < 20% reduction in IOP from the medicated baseline or a IOP of > 21 mmHg at 2 consecutive visits at postoperative month 1 and beyond, the need for subsequent operative intervention or additional glaucoma surgery, or a catastrophic event, such as loss of light perception. Eyes that had not failed by these criteria and were not on glaucoma medications were considered complete successes. Overall success was defined as those who achieved success either with or without topical medications. RESULTS: Patients were followed for an average of 17 months. Complete success was achieved in 42.5% and 24.7% of the open and closed groups, respectively (P = 0.01). Overall success was achieved in 64.2% and 37.0% of the open and closed groups, respectively (P < 0.001) at the last follow-up. Bleb needling was performed in 12.4% of eyes in the open group compared with 40% of eyes in the closed group. An IOP spike of ≥ 10 mmHg was twice as likely to occur in the closed group compared with the open group during the postoperative period (40% vs. 18%; P = 0.001). CONCLUSIONS: Implantation of XEN45 with opening of the conjunctiva resulted in a lower IOP with greater success and lower needling rate compared with those achieved with the closed conjunctiva technique. Similar rates of postoperative complications and vision loss were noted in each group. Although both procedures provide substantial IOP reduction, the open technique appears to result in higher success rates and fewer postoperative interventions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparing Ahmed-FP7 to Baerveldt-250 and Baerveldt-350 surgical outcomes: 1-year results from a retrospective cohort study leveraging the electronic health record.

OBJECTIVE: To compare outcomes following Ahmed-FP7 (AGI-FP7), Baerveldt-250mm2 (BGI-250), or Baerveldt-350mm2 (BGI-350) implantation. METHODS AND ANALYSIS: Retrospective cohort study comprising 800 eyes from 800 individuals who underwent surgery 1 January 2016-31 December 2020 at a tertiary-care institution. Data were extracted from standardised fields in the electronic health record. Primary outcome was failure (defined as intraocular pressure (IOP) ≤5 mm Hg or >18 mm Hg or reduction <20% at two consecutive visits from month 3 onwards; or visual acuity (VA) loss ≥3 lines; or return to the operating room (OR)). Secondary outcomes were IOP, VA, number of follow-up visits and return to the OR. RESULTS: A total of 523 AGI-FP7, 133 BGI-250 and 144 BGI-350 cases were analysed. The AGI-FP7 group was more likely to be younger and diagnosed with secondary glaucoma, with a higher mean baseline IOP (28.5±12.2 vs 22.0±7.7 mm Hg in BGI-250 and 23.4±9.0 in BGI-350, p<0.001). Cumulative failure rate at month 12 was 30% (AGI-FP7) vs 39% (BGI-250) vs 33% (BGI-350, p=0.159). Mean IOP at month 12 was lower in the BGI-350 group compared with AGI-FP7 (12.4±4.4 vs 14.8±5.6 mm Hg, p=0.003) but not BGI-250 (vs 13.1±4.6, p=0.710). Target IOP was achieved in 71% of AGI-FP7, 66% BGI-250, and 76% BGI-350. VA loss and rates of return to the OR did not differ between groups. Both BGI-250 and BGI-350 had more follow-up visits than AGI-FP7 (p<0.001). CONCLUSION: These three glaucoma drainage devices performed similarly within 1 year, with no difference in failure rates despite differing baseline patient characteristics.

Maternity and family leave experiences among female ophthalmologists in the United States.

OBJECTIVE: To evaluate family and maternity leave policies and examine the social and professional impacts on female ophthalmologists. PARTICIPANTS: Participants were recruited through the Women in Ophthalmology online list-serv to complete a survey evaluating maternity leave policies and their impacts. Survey questions were repeated for each birth event after medical school for up to five birth events. RESULTS: The survey was accessed 198 times, and 169 responses were unique. Most participants were practicing ophthalmologists (92%), with a minority in residency (5%), in fellowship (1.2%), on disability/leave (0.6%), or retired (0.6%). Most participants (78%) were within their first ten years of practice. Experiences were recorded for each leave event, with 169 responses for the first leave, 120 for the second, 28 for the third, and 2 for the fourth. Nearly half of participants reported the information they received about maternity leave to be somewhat or extremely inadequate (first: 50%; second: 42%; third: 41%). Many reported a greater sense of burnout after returning to work (first: 61%, second: 58%, third: 46%). A minority of participants received full pay during the first through third maternity leave events, 39%, 27%, and 33%, respectively. About a third of participants reported being somewhat or very dissatisfied with their maternity leave experience (first: 42%, second: 35%; third: 27%). CONCLUSIONS: Female ophthalmologists have varying experiences with maternity leave, but many encounter similar challenges. This study demonstrates that many women receive inadequate information about family leave, desire more weeks of leave, experience a wide variation in pay practices, and lack support for breastfeeding. Understanding the shared experiences of women in ophthalmology identifies areas where improvements are needed in maternity leave practices within the field to create a more supportive environment for physician mothers.

The utility of home tonometry for peri-interventional decision-making in glaucoma surgery: Case series.

Purpose: To describe twelve cases in which home intraocular pressure (IOP) monitoring complimented clinical decision-making in glaucoma management. Observations: Home IOP monitoring elucidated peaks and amplitudes of variation that were not captured by in-clinic IOP measurements during the pre- or post-interventional period. Conclusions & Importance: Home monitoring can establish pre-treatment IOP patterns that are not evident during in-clinic measurements. Home monitoring can also demonstrate response to treatment more quickly than in-clinic monitoring, and provide more information about nyctohemoral fluctuations than is ascertained by in-clinic tonometry.

Electronically Monitored Corticosteroid Eye Drop Adherence after Trabeculectomy Compared to Surgical Success.

PURPOSE: To compare electronically measured adherence with topical corticosteroid (CS) drops with outcomes of glaucoma surgery. DESIGN: This prospective cohort study included eyes undergoing surgery from August 2019 to January 2021 and followed for up to 1 year. PARTICIPANTS: All patients were recruited from the Glaucoma Center of Excellence at the Wilmer Eye Institute, Johns Hopkins. Eligible patients had primary open-angle or angle-closure glaucoma, were aged ≥18 years, and underwent trabeculectomy (with or without cataract surgery) or tube-shunt implantation. METHODS: Patients were instructed on the use of an eye drop monitoring device (Kali Drop), with the knowledge that it would be used to record postoperative CS instillation in real time. MAIN OUTCOME MEASURES: Adherence to a regimen of CS eye drops during the first 5 postoperative weeks; achievement of target intraocular pressure (IOP) at 6 weeks and 6 months to 1 year after surgery; and bleb morphology at 1 year. RESULTS: Among 90 patients, adherence was 89.7% ± 13.7% overall and 80.9% ± 15.8% during dosing every 2 hours. Target IOP was achieved at the final visit (6 months or 1 year) in 81% (59/73) without reoperation. Eyes with a higher ratio of drops taken versus prescribed were significantly more likely to achieve target IOP at 6 months/1 year (P = 0.05). Total adherence was better in younger persons, eyes with less field loss, and patients of one particular surgeon (P < 0.03). Percent adherence during dosing every 2 hours was higher in eyes with higher target IOP (P = 0.01). No adherence outcome was significantly related to race, sex, bleb morphology, postoperative pain, or postoperative anterior chamber inflammation. Adherence values did not significantly correlate with adherence questionnaire data (predicted mean = 78% ± 17%, actual mean = 91% ± 13% adherent, P < 0.001). CONCLUSIONS: Adherence to frequent postoperative eye drops was high and can be successfully monitored remotely. Surgical success was greater among eyes with nearly ideal adherence and was poorer in older persons and those with more advanced glaucoma.

Home Self-tonometry Trials Compared with Clinic Tonometry in Patients with Glaucoma.

PURPOSE: This study examined characteristics of intraocular pressure (IOP) as measured during home tonometry in comparison with in-clinic tonometry in patients with glaucoma. DESIGN: Retrospective cross-sectional study of glaucoma patients who completed 1 week of self-tonometry at a single academic center. PARTICIPANTS: Patients with glaucoma who completed home tonometry trials with the iCare HOME tonometer (iCare USA) for any reason. METHODS: Home IOP measurements were compared with in-clinic tonometry performed during the 5 visits preceding home tonometry. Maximum daily IOP was correlated to time of day. Generalized estimating equations were used to evaluate patient characteristics and clinic-derived variables that predicted differences between home and clinic IOP. MAIN OUTCOME MEASURES: IOP mean, maximum, minimum, range, standard deviation and coefficient of variation were compared between clinic and home tonometry. IOP mean daily maximum (MDM) and mean daily range were calculated to describe recurrent IOP spiking. RESULTS: A total of 107 eyes from 61 patients were analyzed. Mean age was 63.2 years (standard deviation [SD], 14.0 years) and 59.0% were women. Mean clinic and home IOPs were 14.5 mmHg (SD, 4.7 mmHg) and 13.6 mmHg (SD, 5.1 mmHg). Home tonometry identified significantly higher maximum IOP, lower minimum IOP, and greater IOP range than clinic tonometry (P < 0.001). Maximum daily IOP occurred outside of clinic hours (8 am-5 pm) on 50% of days assessed and occurred between 4:30 am and 8 am on 24% of days. Mean daily maximum IOP exceeded maximum clinic IOP in 44% of patients and exceeded target IOP by 3 mmHg, 5 mmHg, or 10 mmHg in 31%, 15%, and 6% of patients, respectively. Patient characteristics that predicted significant deviations between MDM and mean clinic IOP or target IOP in multivariate models included younger age, male gender, and absence of prior filtering surgery. CONCLUSIONS: Self-tonometry provides IOP data that supplements in-clinic tonometry and would not be detectable over daytime in-clinic diurnal curves. A subset of patients in whom home tonometry was ordered by their glaucoma clinician because of suspicion of occult IOP elevation demonstrated reproducible IOP elevation outside of the clinic setting. Such patients tended to be younger and male and not to have undergone previous filtering surgery.

Pilot Study of Audiometric Patterns in Fuchs Corneal Dystrophy.

Purpose: Although Fuchs corneal dystrophy (FCD) is considered an eye disease, a small number of studies have identified genes related to both FCD and hearing loss. Whether FCD is related to hearing loss is unknown. Method: This is a case-control study comparing pure-tone audiometry hearing thresholds in 180 patients with FCD from a hospital-based ophthalmology clinic with 2,575 population-based controls from a nationally representative survey, the National Health and Nutrition Examination Survey (from cycles 2005-06 and 2009-10). Generalized estimating equations were used to compare mean better-hearing ear thresholds in the 2 groups adjusted for age, sex, race, and noise exposure. Results: Patients with FCD had higher hearing thresholds (worse hearing) in lower frequencies (mean difference at 0.5 kHz = 3.49 dB HL) and lower hearing thresholds (better hearing) in higher frequencies (difference at 4 kHz = -4.25 dB HL) compared with population-based controls. Conclusion: In the first study to use objectively measured hearing, FCD was associated with poorer low-frequency and better high-frequency audiometric thresholds than population controls. Further studies are needed to characterize this relationship.

Predictive Value of Corneal Donor Demographics on Endothelial Cell Density.

PURPOSE: Corneal endothelial cell density (ECD) is an important measure for determining suitability for transplantation. Although age has been correlated with ECD, the impact of sex and ethnicity is unclear. METHODS: Corneal donor information from SightLife Eye Bank was collected between 2012 and 2016. Tests of association were adjusted for covariates using linear regression including age, race, and sex. "Unsuitable for transplantation" was a label assigned to specimens with extensive cell dropout, ECD <2000 cells/mm, and poor cell morphology. Repeated-measures analysis was used to account for the within-individual correlation between left and right eyes. RESULTS: A total of 39,679 donor corneas were analyzed, with a mean ECD 2743.5 cells/mm and mean age of 58. Simple linear regression demonstrated an association between ECD and age (P < 0.001). Multiple regression showed no association between sex and ECD. Compared with whites, African American, and Asian ethnicities were predictors of increased ECD (mean +45.7 cells/mm (P < 0.001) and +90.3 cells/mm (P < 0.001), respectively); Hispanic ethnicity was a predictor of decreased ECD [mean -36.9 cells/mm (P = 0.002)]. A total of 233 (0.59%) corneas were unsuitable for transplantation, which was associated with age (P < 0.001) but not sex or ethnicity. CONCLUSIONS: Analysis of a large sample of donor corneas continues to show age but not sex as a predictor of decreased ECD. African American and Asian ethnicities tend to have slightly higher ECD than that of white donors, whereas Hispanic donors have slightly lower ECD; however, ethnicity was not a predictor of suitability for transplantation. Clinical significance of these findings is yet to be determined.

Recurrent Corneal Erosions Secondary to Use of Sleep Mask.

A 31-year-old woman with a history of unusual appearing recurrent linear corneal epithelial defects and subepithelial scaring in both eyes underwent 2 years of evaluation and treatment. It was eventually discovered that the patient was using a sleep mask with excessive fabric pilling, which was found to be the source of her chronic epitheliopathy. After discontinuation of the sleep mask, the patient experienced complete resolution of symptoms. When evaluating recurrent corneal epithelial defects, external sources of repeated trauma, including sleepwear, should be investigated.

Retroillumination Photography Analysis Enhances Clinical Definition of Severe Fuchs Corneal Dystrophy.

PURPOSE: Retroillumination photography analysis (RPA) provides an objective assessment of the number and distribution of guttae in Fuchs corneal dystrophy. Here, we assess its correlation with clinical grading using slit-lamp biomicroscopy across varying levels of severity. METHODS: Retroillumination photographs were conducted for 95 affected corneas with slit-lamp flash photography after pupillary dilation. Individual guttae were counted manually and the position of individual points recorded. Clinical grading using the Krachmer scale was documented for each eye during examination, and regression analyses were performed to identify the strength of association with number of guttae. We assessed range at each stage of clinical grading and used the Mann-Whitney U test to assess whether clinical grading levels demonstrated successively higher numbers of guttae. RESULTS: Krachmer score ranged from 1 to 5, with mean of 2.6. Mean numbers of guttae at each level of severity were 289 (1+), 999 (2+), 2669 (3+), 5474 (4+), and 7133 (5+). Each stage demonstrated significantly higher numbers of guttae than its preceding level except from 4+ to 5+ (P = 0.30), consistent with the definition of 4+ as the highest level defined by the presence of guttae. Higher levels of clinical grading were associated with larger ranges of guttae (P < 0.01). A linear regression model resulted in a strong fit between RPA and Krachmer score (r = 0.81). CONCLUSIONS: In this largest study of RPA data and comparison with subjective clinical grading of Fuchs dystrophy severity, RPA correlates strongly and demonstrates enhanced definition of severity at advanced stages of disease.

Mutations in LOXHD1, a recessive-deafness locus, cause dominant late-onset Fuchs corneal dystrophy.

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes.

Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

PURPOSE: To investigate the clinical and genetic features of late-onset Fuchs corneal dystrophy (FCD) on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals. DESIGN: Observational, cross-sectional study. METHODS: A total of 156 individuals born to inhabitants of Tangier Island volunteered to undergo ophthalmic evaluation. Medical history was ascertained prior to examination. All participants underwent anterior segment examination with slit-lamp biomicroscopy. Retroillumination photographs were acquired from affected individuals and the disease severity was compared with individuals from large families ascertained previously. Genomic DNA samples were investigated for the presence of the recently identified risk allele rs613872, an intronic variant of TCF4. RESULTS: Of the 148 examined individuals who were at least 30 years of age, 32 showed the classical symptoms of late-onset FCD (21.6%), providing a minimum prevalence of 11% among individuals over the age of 50 years. Severity was significantly lower compared to 51 cases from unlinked families, among individuals either 50 to 70 or above 70 years of age (P = .05 and P = .01, respectively). Retroillumination photography analyses were suggestive of mild severity when compared with the disease phenotype associated with FCD1- and FCD2-linked families. The rs613872 variant was associated with a higher affectation rate (P = .01), while the wild-type allele was correlated with a higher proportion of subclinical disease (P = .01). CONCLUSIONS: In this study population in Tangier, late-onset FCD manifests clinically with a mild phenotype and increased prevalence. The rs613872 variant correlates with increased affectation and a clinical disease phenotype.

Replication of the TCF4 intronic variant in late-onset Fuchs corneal dystrophy and evidence of independence from the FCD2 locus.

PURPOSE: Fuchs corneal dystrophy (FCD) is an autosomal dominant disease of the corneal endothelium with variable penetrance and expressivity. Recently, rs613872, an intronic variation of TCF4 associated with late-onset FCD, was reported. The present study was undertaken to examine this association in our cohort of FCD patients, to assess the significance of this finding, and to investigate the candidacy of TCF4 in the context of the mapped FCD2 locus. METHODS: The authors recruited 170 patients with late-onset FCD and 180 age-matched controls. Blood samples were collected, and genomic DNA was extracted. A panel of nine SNPs spanning the entire TCF4 locus was genotyped both on this cohort and on three previously reported FCD2-linked families. The association of an individual SNP with late-onset FCD was evaluated with the Fisher exact test, and the coding exons and exon-intron boundaries of TCF4 were sequenced in 96 affected persons. RESULTS: The risk allele G of rs613872 is associated significantly with late-onset FCD (odds ratio, 4.2; P = 4.28 x 10⁻¹5) and was present in male and female affected persons without any sex bias, replicating recent findings, though the authors found no apparent correlation with the severity of the disease phenotype. Moreover, the risk allele did not cosegregate with the disease phenotype in any of the three FCD2-linked families. The authors did not identify any pathogenic variants in the coding region of TCF4. CONCLUSIONS: The authors report the first independent replication of rs613872 conferring risk of late-onset FCD. Their data suggest that this risk factor is likely independent of the FCD2 locus, whose causality remains unknown.

Age-severity relationships in families linked to FCD2 with retroillumination photography.

PURPOSE: Fuchs corneal dystrophy (FCD) is a progressive disorder of the corneal endothelium and is pathologically defined by the presence of guttae, which are excrescences of the Descemet membrane. The present study was undertaken to investigate the age-severity relationship of the FCD2-linked disease phenotype using retroillumination photography and to compare it with the characteristics of FCD1. METHODS: Two large families with multiple affected members were recruited. Exclusion analyses of the known late-onset FCD loci were completed with closely spaced STR markers, whereas genes associated with early- and late-onset FCD were investigated by bidirectional sequencing. Haplotypes were constructed, and two-point LOD scores were calculated. To document age-severity relationships, retroillumination photographs were acquired from members of both families. RESULTS: Parametric linkage and haplotype analysis mapped both families to FCD2 with significant two-point LOD scores. A total of 70,249 guttae were counted in 14 persons from both families. A significant increase in guttae density in the inferotemporal region (P = 0.016) was observed, a pattern similarly observed in a family linked to FCD1. Similarly, FCD2-linked families display an exponential trend in severity with age, as was observed in a family linked to FCD1. Finally, comparison of FCD1 and FCD2 exponential models suggested that the FCD1 phenotype is significantly more severe (P = 0.01). CONCLUSIONS: A combination of genetic mapping and retroillumination photography was used to quantify the severity of the disease phenotype associated with FCD2 and to compare it to the disease characteristics of FCD1. These data suggest that this approach might have sufficient resolution to discriminate between discrete genetic FCD backgrounds, which will potentially aid in patient management.