Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A deep dive into hyperbaric environments and intraocular pressure-a systematic review.

Purpose: SCUBA diving exposes participants to a unique hyperbaric environment, but few studies have examined the effects of such an environment on intraocular pressure (IOP) and glaucoma. This systematic review aims to consolidate recent literature findings regarding the impact of increased atmospheric pressure on IOP and glaucoma. Methods: Three online databases were searched to identify publications encompassing the subjects of diving or increased atmospheric pressure in conjunction with IOP or glaucoma. Three reviewers independently screened the publications and identified eligible articles. Relevant data was extracted from each article. The heterogeneity of the data precluded the conduct of a meta-analysis. Results: Nine studies met the inclusion criteria. Six experimental studies employed hyperbaric chambers to measure IOP under simulated diving conditions. Among these, IOP exhibited a reduction with increased atmospheric pressures in four studies, while the findings of two studies were inconclusive. One study measured IOP pre- and post-dive and another measured IOP with and without a diving mask. Post-dive, a decrease in IOP was observed, and a statistically significant reduction was noted when subjects wore a diving mask. A retrospective study examining the incidence of acute angle closure glaucoma attack found no association with weather or atmospheric pressure. Conclusion: The majority of studies found IOP to decrease with increased atmospheric pressure and after diving. The mechanisms underlying this reduction remain incompletely understood, with potential contributors including changes in ocular blood flow, sympathetic responses, and increased oxygenation. Hyperbaric chambers may have potential in future glaucoma treatments, but more studies are required to draw reliable conclusions regarding the safety of diving for glaucoma patients.

Long-Term Efficacy of Successful Excisional Goniotomy with the Kahook Dual Blade.

Purpose: To report clinical outcomes of successful excisional goniotomy with the Kahook Dual Blade (KDB), through 60 months. Patients and methods: This was a noncomparative, single-surgeon, retrospective review of eyes receiving successful KDB goniotomy with or without concomitant phacoemulsification between October 2015 and January 2016 with five years of uninterrupted follow-up. Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), and complications were recorded. Primary outcomes included changes from baseline in IOP, medication use, and BCVA, through five years. Results: Fifty-two eyes of 28 patients were analyzed. Most eyes had mild primary open angle glaucoma (73%). Of the eyes analyzed, 41 underwent combined surgery and 11 underwent standalone surgery. With all eyes combined, mean (standard deviation) baseline IOP was 21.0 (4.1) mmHg and mean baseline medication use was 1.8 (1.1) medications per eye. Across time points at months 6, 12, 24, 36, 48, and 60, mean postoperative IOP ranged from 13.0 to 13.7 mmHg, representing mean reductions of 7.3-8.0 mmHg (34.7-38.3%; p <0.0001 at every time point). Similarly, mean medication use ranged from 0.4 to 0.6 medications per eye, representing mean reductions of 1.2-1.4 medications (66-75.5%; p <0.0001 at every time point). Mean logMAR BCVA improved from 0.321 (0.177) preoperatively to 0.015 (0.035) at month 60 (p < 0.0001). Conclusion: In eyes not requiring secondary surgical procedures (eg, long-term surgical successes), excisional goniotomy provided clinically and statistically significant reductions in both IOP and the need for medications that were highly consistent through five years of follow-up. KDB goniotomy appears to be highly successful in Caucasian patients with open angle glaucoma on ≥1 IOP-lowering medications at baseline and with no history of prior ocular surgery. Successful excisional goniotomy with the KDB can be expected to improve long-term glaucoma-related visual outcomes through IOP reduction and to improve quality of life through medication reduction.

Advanced Corneal Imaging in Keratoconus: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus. METHODS: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%. CONCLUSIONS: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating Access to Laser Eye Surgery by Driving Times Using Medicare Data and Geographical Mapping.

Importance: Recently, several states have granted optometrists privileges to perform select laser procedures (laser peripheral iridotomy, selective laser trabeculoplasty, and YAG laser capsulotomy) with the aim of increasing access. However, whether these changes are associated with increased access to these procedures among each state's Medicare population has not been evaluated. Objective: To compare patient access to laser surgery eye care by estimated travel time and 30-minute proximity to an optometrist or ophthalmologist. Design, Setting, and Participants: This retrospective cohort database study used Medicare Part B claims data from 2016 through 2020 for patients accessing new patient or laser eye care (laser peripheral iridotomy, selective laser trabeculoplasty, YAG) from optometrists or ophthalmologists in Oklahoma, Kentucky, Louisiana, Arkansas, and Missouri. Analysis took place between December 2021 and March 2023. Main Outcome and Measures: Percentage of each state's Medicare population within a 30-minute travel time (isochrone) of an optometrist or ophthalmologist based on US census block group population and estimated travel time from patient to health care professional. Results: The analytic cohort consisted of 1 564 307 individual claims. Isochrones show that optometrists performing laser eye surgery cover a geographic area similar to that covered by ophthalmologists. Less than 5% of the population had only optometrists (no ophthalmologists) within a 30-minute drive in every state except for Oklahoma for YAG (301 470 [7.6%]) and selective laser trabeculoplasty (371 097 [9.4%]). Patients had a longer travel time to receive all laser procedures from optometrists than ophthalmologists in Kentucky: the shortest median (IQR) drive time for an optometrist-performed procedure was 49.0 (18.4-71.7) minutes for YAG, and the the longest median (IQR) drive time for an ophthalmologist-performed procedure was 22.8 (12.1-41.4) minutes, also for YAG. The median (IQR) driving time for YAG in Oklahoma was 26.6 (12.2-56.9) for optometrists vs 22.0 (11.2-40.8) minutes for ophthalmologists, and in Arkansas it was 90.0 (16.2-93.2) for optometrists vs 26.5 (11.8-51.6) minutes for ophthalmologists. In Louisiana, the longest median (IQR) travel time to receive laser procedures from optometrists was for YAG at 18.5 (7.6-32.6) minutes and the shortest drive to receive procedures from ophthalmologists was for YAG at 20.5 (11.7-39.7) minutes. Conclusions and Relevance: Although this study did not assess impact on quality of care, expansion of laser eye surgery privileges to optometrists was not found to lead to shorter travel times to receive care or to a meaningful increase in the percentage of the population with nearby health care professionals.

Differences in characteristics of Medicare patients treated by ophthalmologists and optometrists.

PURPOSE: To quantify differences in the age, gender, race, and clinical complexity of Medicare beneficiaries treated by ophthalmologists and optometrists in each of the United States. DESIGN: Cross-sectional study based on publicly accessible Medicare payment and utilization data from 2012 through 2017. METHODS: For each ophthalmic and optometric provider, demographic information of treated Medicare beneficiaries was obtained from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS) for the years 2012 through 2017. Clinical complexity was defined using CMS Hierarchical Condition Category (HCC) coding. RESULTS: From 2012 through 2017, ophthalmologists in every state treated statistically significantly older beneficiaries, with the greatest difference (4.99 years in 2014) between provider groups seen in Rhode Island. In most states there was no gender difference among patients treated by the providers but in 46 states ophthalmologists saw a more racially diverse group of beneficiaries. HCC risk score analysis demonstrated that ophthalmologists in all 50 states saw more medically complex beneficiaries and the differences were statistically significant in 47 states throughout all six years. CONCLUSIONS: Although there are regional variations in the characteristics of patients treated by ophthalmologists and optometrists, ophthalmologists throughout the United States manage older, more racially diverse, and more medically complex Medicare beneficiaries.

Recurrent corneal erosion: a comprehensive review.

PURPOSE: To comprehensively review the literature regarding recurrent corneal erosion (RCE) and to present treatment options and recommendations for management. OVERVIEW: RCE usually presents with sharp, unilateral pain upon awakening, in an eye with an underlying basement membrane dystrophy, prior ocular trauma, stromal dystrophy or degeneration, or prior surgery for refractive errors, cataracts, or corneal transplantation. Making the correct diagnosis requires a careful slit-lamp examination of both eyes coupled with a high degree of suspicion. Several treatments are commonly used for RCE but new therapies have been introduced recently. Conservative treatment consists of antibiotic and preservative-free lubricating drops, with topical cycloplegics and oral analgesics to control pain. Patients who are unresponsive to these therapies may benefit from therapeutic bandage contact lenses (BCL). Newer therapies include oral matrix metalloproteinase (MMP) inhibitors, blood-derived eye drops, amniotic membrane graft application, and judicious application of topical corticosteroids. Once the epithelium is healed, a course of hypertonic saline solution and/or ointment can be used. Surgical procedures may be performed in patients who fail conservative therapy. Punctal occlusion with plugs increases the tear film volume. Epithelial debridement with diamond burr polishing (DBP), anterior stromal puncture (ASP), or alcohol delamination should be considered in selected patients. DBP can be used for patients with basement membrane dystrophies and is the preferred treatment overall due to a low recurrence rate. ASP can be used for erosions outside the central visual axis. Excimer laser phototherapeutic keratectomy is an attractive option in eyes with central RCE since it precisely removes tissue while preserving corneal transparency. In patients with RCE who are also candidates for refractive surgery, photorefractive keratectomy can be considered. SUMMARY: Newly introduced therapies for RCE enable therapy to be individualized and lower the recurrence rate.

Diagnosis of dry eye disease and emerging technologies.

Dry eye is one of the most commonly encountered problems in ophthalmology. Signs can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear break-up time, and meibomian gland disease. Current methods of diagnosis include a slit-lamp examination with and without different stains, including fluorescein, rose bengal, and lissamine green. Other methods are the Schirmer test, tear function index, tear break-up time, and functional visual acuity. Emerging technologies include meniscometry, optical coherence tomography, tear film stability analysis, interferometry, tear osmolarity, the tear film normalization test, ocular surface thermography, and tear biomarkers. Patient-specific considerations involve relevant history of autoimmune disease, refractive surgery or use of oral medications, and allergies or rosacea. Other patient considerations include clinical examination for lid margin disease and presence of lagophthalmos or blink abnormalities. Given a complex presentation and a variety of signs and symptoms, it would be beneficial if there was an inexpensive, readily available, and reproducible diagnostic test for dry eye.

Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis.

PURPOSE: To compare qualitatively and quantitatively Optos fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in patients with uveitis. DESIGN: Retrospective, observational case series. METHODS: Images of all patients with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9-month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage. RESULTS: The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P < 0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25% less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were 2 eyes that had no apparent retinal vascular leakage in 9-field montage but were found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the Optos image. A single 200-degree Optos FA image captured a mean 1.50× the area captured by montage photography. CONCLUSIONS: More retinal vascular pathology, in both the periphery and the posterior pole, is seen with Optos FA in patients with uveitis when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.

Route of adenovirus-based HIV-1 vaccine delivery impacts the phenotype and trafficking of vaccine-elicited CD8+ T lymphocytes.

Candidate HIV-1 vaccine regimens utilizing intramuscularly (i.m.) administered recombinant adenovirus (rAd)-based vectors can induce potent mucosal cellular immunity. However, the degree to which mucosal rAd vaccine routing might alter the quality and anatomic distribution of vaccine-elicited CD8(+) T lymphocytes remains unclear. We show that the route of vaccination critically impacts not only the magnitude but also the phenotype and trafficking of antigen-specific CD8(+) T lymphocytes in mice. I.m. rAd immunization induced robust local transgene expression and elicited high-frequency, polyfunctional CD8(+) T lymphocytes that trafficked broadly to both systemic and mucosal compartments. In contrast, intranasal (i.n.) rAd immunization led to similarly robust local transgene expression but generated low-frequency, monofunctional CD8(+) T lymphocytes with restricted anatomic trafficking patterns. Respiratory rAd immunization elicited systemic and mucosal CD8(+) T lymphocytes with phenotypes and trafficking properties distinct from those elicited by i.m. or i.n. rAd immunization. Our findings indicate that the anatomic microenvironment of antigen expression critically impacts the phenotype and trafficking of antigen-specific CD8(+) T lymphocytes.