Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (<5% to 15%) and average image interpretation time (1-5 days). Patient education, resource availability, and infrastructural support were identified as barriers to DR teleretinal screening. Cost and integration into existing technology infrastructures were identified as barriers to AI integration in DR screening. Conclusions: Despite the potential to increase access to care, there remain several barriers to widespread implementation of DR teleretinal screening. More research is needed to develop best practices to overcome these barriers.

Background To evaluate the relationship between the presence of an acquired pit of the optic nerve (APON) and the rate of visual field (VF) decay in primary open-angle glaucoma (POAG). Methods Consecutive patients with POAG were screened for APON by three glaucoma specialists. A control group of POAG eyes without APON were matched with the APON group for factors such as age, gender, baseline intraocular pressure and baseline mean deviation (MD). The pointwise rate of change (PRC) was used for pointwise comparisons between the two groups. MD rate, Visual Field Index (VFI) rate and Glaucoma Rate Index (GRI) were used for global rate comparisons. We compared the proportions of eyes progressing in the groups with event-based guided progression analysis (GPA), MD, VFI and GRI criteria. Results Mean (SD) PRC was faster in the APON group −1.00 (±2.57) %/year compared with the control group −0.25 (±2.19) %/year; p<0.001. MD rate (−0.22 (±0.27) dB/year vs 0.03 (±0.41) dB/year; p=0.009), VFI rate (−0.81 (±0.86) %/year vs −0.05 (±1.0) %/year; p=0.04) and GRI (−12.27 (±16.27) vs -3.75 (±10.6); p=0.052) were all faster in the APON group compared with controls. The proportion of progressing eyes with GPA, MD, VFI and GRI was not significantly different between the two groups (p>0.1). Conclusions The presence of APON in patients with POAG is associated with focal, fast rates of VF decay. Identification of patients with APON should alert clinicians to the possibility of a fast rate of functional progression and to consider appropriately aggressive treatment of their glaucoma.

Importance Rates of visual field (VF) progression vary among patients with glaucoma. Knowing the rate of progression of individual patients would allow appropriately aggressive therapy for patients with high rates of visual loss and protect those with low rates from unnecessary therapy. Objective To compare 3 pointwise methods of estimating the rate of VF progression in glaucoma. Design, Setting, and Participants This retrospective, observational cohort study included 729 eyes of 567 consecutive patients with primary open-angle glaucoma who had at least 6 reliable VFs and at least 3 years of follow-up. One hundred seventy-six patients (257 eyes) were treated at a tertiary glaucoma center; in addition, data were collected from 391 participants (472 eyes) in the Advanced Glaucoma Intervention Study. Data were collected from May 1988 to November 2004 and analyzed from October 2018 to February 2019. Exposures Estimates of VF progression were measured with guided progression analysis (GPA), pointwise linear regression (PLR), and the glaucoma rate index (GRI). A subgroup analysis was performed in a subset of patients with likely VF progression and likely VF stability. Main Outcomes and Measures Proportion of VF series detected as progressing, estimates of false-positive proportions, time to detect progression, and agreement among measures. Results Among the 567 patients included in the analysis, mean (SD) age was 65.6 (9.7) years, 300 (52.9%) were female, and 295 (52.0%) were white. The median baseline mean deviation was -6.7 (interquartile range [IQR], -11.6 to -3.5) dB; the median follow-up time, 8.9 (IQR, 7.3-10.4) years. The proportion of eyes labeled as progressing was 27.7% according to the GPA, 33.5% according to the PLR, and 52.9% according to the GRI; pairwise differences for GRI vs PLR were 20% (95% CI, 17%-23%); for GRI vs GPA, 25% (95% CI, 22%-29%); and for PLR vs GPA, 6% (95% CI, 3%-9%; P < .001 for all comparisons, McNemar test). The shortest median time to progression was with the GRI (8.8 [IQR, 2.4-10.5 years), compared with the GPA and PLR (both >16 years). The hazard ratio of VF progression for GRI vs PLR (reference) was 11.3 (95% CI, 9.2-13.7); for GRI vs GPA (reference), 18.1 (95% CI, 14.5-22.6); and for PLR vs GPA (reference), 1.5 (95% CI, 1.3-1.9; P < .001 for all comparisons, Cox proportional hazards regression). These results held in the subgroup with likely progression; the proportions of progressing eyes were 73.7% (115 of 156) for GPA, 81.4% (127 of 156) for PLR, and 92.9% (145 of 156) for GRI. Pairwise difference for GRI vs PLR was 11.5% (95% CI, 7.4%-17.6%; P < .001, McNemar test); for GRI vs GPA, 19.2% (95% CI, 12.6%-26.4%; P < .001, McNemar test); and for PLR vs GPA, 7.7% (95% CI, 0.3%-15.7%; P = .08, McNemar test). Conclusions and Relevance These results suggest GRI can detect long-term VF progression in glaucoma earlier than PLR or GPA. Validation with prospective designs may strengthen the generalizability and value of this method.

To the Editor: We read with great interest the case reported by Lin et al1 of a patient with latanoprost-induced depigmentation. The authors refer that this is the first report documenting such an association. However, we already reported a case of skin depigmentation presumably related to prostaglandin analogs 13 years ago.2 Worsening of skin depigmentation took place at different areas of the body (peribucal, back of the hand, forearm, and proximal part of the thigh) in a white woman with vitiligo, 1 year after therapy with a fixed combination of latanoprost and timolol (Xalacom, Pfizer, New York, NY).2 This drug was withdrawn, but the depigmentation changes did not modify. The patient refused to reintroduce the same therapy, so we could not prove the casual relationship between depigmentation and the therapy. Although we cannot discard the role of timolol or the fixed combination on these skin changes, to the best of our knowledge, there are no reported cases of skin depigmentation related to beta-blockers use. There are several differences between both cases regarding race, sex, predisposing conditions, and area of depigmentation. Lin and colleagues reported significant periocular depigmentation in an African American man probably related with topical exposure to latanoprost. In our case an increase in depigmentation occurred in a white woman affected by vitiligo in previously depigmented areas distant to drug application. Latanoprost induces melanocyte proliferation and melanosomal transfer and it is commonly used in Dermatology to induce repigmentation of the skin and scars. The efficacy and safety of different prostaglandins analogs in periorbital vitiligo has been reported.3 Regarding these aspects, it is difficult to explain the paradoxical effect of depigmentation found in both patients. Lin et al1 suggest a localized postinflammatory hypopigmentation of the skin as potential mechanism. A prostaglandin dual effect on immune response, with an initial phase of stimulation and posterior phase of modulation has been reported under prostaglandin therapy4 and can explain opposite effects in some patients. However, the underlying explanation for these paradoxical effects cannot be elucidated in this moment. Despite the well-known periocular hyperpigmentation side effect related to prostaglandin analogs use, we want to highlight the possibility of paradoxical skin hypopigmentation in some predisposed patients, although further reports are required to confirm their causal relation.

Purpose: Primary open-angle glaucoma (POAG) patients constitute a heterogenous group. Identification of phenotypic subtypes among these patients may provide a deeper understanding of the disease and aid associations with genotypes. We describe a phenotype of POAG patients associated with a constellation of systemic disorders; patients with this phenotype seem to be vulnerable to optic nerve damage at low intraocular pressures. Materials and Methods: In this retrospective study, we evaluated the medical records of active Jules Stein Eye Institute glaucoma patients from January 1996 to 2017 and included subjects with POAG, acquired pits of the optic nerve (APON), and at least one of the following: systolic blood pressure persistently <= 100 mm Hg, history of migraine headaches or migraine variant, and the Raynaud syndrome. Results: Of 87 patients (125 eyes) with APON, 37 patients (55 eyes) met the study criteria. In total, 34 patients were female (92%). The median age at the time of diagnosis was 55 years. Nineteen patients (73%) had low systolic blood pressures, same number had Raynaud syndrome, and 25 (68%) had a history of migraine. Conclusions: We describe a POAG subtype with APON and systemic vascular instability, predominantly female in their sixth decade of life who demonstrate progressive glaucomatous visual field damage at low intraocular pressure. We suggest that this clinical picture represents an important phenotype of POAG, and that identification and further study of it will help guide diagnosis and development of individualized treatments.

Purpose: Evaluate the intraocular pressure (IOP) control in combined Ahmed Glaucoma Valve (AGV) implantation and trabeculectomy revision with adjunctive antimetabolite compared with AGV alone in patients who failed prior trabeculectomy. Methods: Consecutive cases of combined AGV implantation and trabeculectomy revision with adjunctive antimetabolite (combined group) after January 3, 2014 were case-matched to cases of AGV implantation alone (AGV-alone group) before January 3, 2014. Primary outcome measures were qualified success with stratified IOP targets based on criteria: (A) IOP≤18 mm Hg and 20% IOP reduction; (B) IOP≤15 mm Hg and 25% IOP reduction; (C) IOP≤12 mm Hg and 30% IOP reduction, and hypertensive phase (HP) rate. Secondary outcome measures were 1-year postoperative IOP and number of glaucoma medications and complications. Results: Twenty eyes (20 patients) in each group were included. Cumulative success for combined group and AGV-alone group at 1-year were: 74.0% versus 59.2% (criterion A, P=0.221), 61.9% versus 49.5% (B, P=0.183), and 54.2% versus 30.0% (C, P=0.033), respectively. In total, 50% (10 eyes) in the AGV-alone group developed HP compared with 15% (3 eyes) in the combined group (P=0.041). At 1-year follow-up, combined group had statistically significantly lower IOP than AGV-alone group (10.1±4.4, 13.3±2.9 mm Hg, respectively; P=0.028). There were no cases of bleb-related infections, choroidal effusion or hemorrhage, persistent hypotony, or hypotony maculopathy in either group. Conclusions: Combining AGV implantation with trabeculectomy revision with antimetabolite was associated with better tonometric success compared with AGV implantation alone in patients with previously failed trabeculectomy, particularly when a low IOP target (≤12 mm Hg) is required. Revised trabeculectomy may provide complimentary outflow facility to AGV.

Purpose: To compare the assessment of serial visual fields (VFs) based on subjective expert evaluation with the fast and slow VF component rates determined with pointwise exponential regression (PER) and pointwise linear regression (PLR). Materials and Methods: A total of 5272 VF examinations from 376 eyes diagnosed with open-angle glaucoma were included. Three glaucoma specialists assessed each VF qualitatively to evaluate progression status and the qualitative rate of progression. The rates of VF decay were determined with PER and PLR at each VF location, which were ranked according to the regression coefficient and partitioned into 2 groups (fast and slow). A mean rate for the fast and slow partitions was obtained based on the average of the regression coefficients in each partition. κ-values were used to measure the agreement among the experts and the PER and PLR algorithms. Results: The average baseline VF mean deviation for the study sample was −6.6 (±5.9) dB. The agreement of the likelihood of progression among the dichotomized experts’ score and PER was moderate (κ=0.41, P<0.01) and fair (κ=0.39, P<0.01) for PLR. The agreement of the likelihood of progression among the 3 dichotomized experts’ scores was fair (κ=0.22, P<0.01). The agreement of the area of worsening among the dichotomized experts’ score and PER and PLR were both moderate (κ=0.48, P<0.01; κ=0.46, P<0.01). The eyes flagged by experts as having “fast” progression rates had a higher average rates of decay for PER and PLR at −2.7 (±4.1) %/year and −0.8 (±1.2) dB/year; eyes flagged as “slow” had lower rates of decay at −0.3 (±1.5) %/year and −0.1 (±0.5) dB/year. Conclusions: Expert qualitative evaluation of field series for change and rate of change correlate more closely with the fast component than with the slow component of VF decay.

IMPORTANCE:The loss of vision following Boston Keratoprosthesis (BKPro) surgery due to glaucoma occurs at a high frequency as diagnosis and management of glaucoma after this procedure pose challenges.OBJECTIVE:To compare visual outcomes in patients undergoing Boston Keratoprosthesis surgery with and without prior or concurrent glaucoma surgery.DESIGN, SETTING, AND PARTICIPANTS:This is a retrospective, observational cohort study of patients who underwent Boston Type I Keratoprosthesis surgery. 19 eyes of 18 patients who had undergone BKPro and met the inclusion criteria were identified. Twelve eyes received BKPro with prior or concurrent glaucoma surgery (Group 1), and seven eyes were identified undergoing BKPro surgery without prior or concurrent glaucoma surgery (Group 2).MAIN OUTCOMES AND MEASURES:Main outcome included best corrected visual acuity at each follow up.RESULTS:In Group 1, mean best corrected visual acuity (BCVA) within a year of BKPro surgery was 20/100 (range 20/40 to Count Fingers (CF); n = 12) and mean BCVA at 1 year from BKPro surgery was 20/115 (range 20/30 to CF; n = 12). 7 out of 12 patients retained or had improved BCVA at 1 year follow up after BKPro implantation, and 5 out of 12 patients had mild BCVA worsening. In Group 2, the mean BCVA within a year of BKPro surgery was 20/140 (ranging from 20/25 to hand motion vision (HM); n = 7) and mean BCVA at 1 year from BKPro surgery was Count Fingers (range 20/60 to Light Perception (LP); n = 6). 4 out of 6 patients lost significant vision at one year after BKPro.CONCLUSIONS AND RELEVANCE:BKPro patients with early glaucoma surgical intervention retained vision significantly better compared to patients with late or no intervention. Our preliminary findings support the recommendation for concurrent or pre-emptive glaucoma surgical intervention in patients undergoing BKPro implantation.

Latanoprost, and other prostaglandin analogs, have been previously associated with increased pigmentary reactions on the periocular skin. Here, we present a patient with paradoxical depigmentation of periocular skin within 1 year of latanoprost use in both eyes. This report is the first to document such an association, and clinicians should be aware of this adverse effect and monitor for signs accordingly.

T-cell-dependent antigenic stimulation drives the differentiation of B cells into antibody-secreting plasma cells and memory B cells, but how B cells regulate this process is unclear. We show that LKB1 expression in B cells maintains B-cell quiescence and prevents the premature formation of germinal centers (GCs). Lkb1-deficient B cells (BKO) undergo spontaneous B-cell activation and secretion of multiple inflammatory cytokines, which leads to splenomegaly caused by an unexpected expansion of T cells. Within this cytokine response, increased IL-6 production results from heightened activation of NF-κB, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (TFH ) cell differentiation and expansion to support a ~100-fold increase in steady-state GC B cells. Blockade of IL-6 secretion by BKO B cells inhibits IL-21 expression, a known inducer of TFH -cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control TFH -cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity.