RANDOMIZED TRIAL COMPARING MICROSERRATED VERSUS CONVENTIONAL INTERNAL LIMITING MEMBRANE FORCEPS FOR INTERNAL LIMITING MEMBRANE PEELING.

PURPOSE: To evaluate anatomic outcomes and surgeon response following the use of microserrated (Sharkskin, Alcon, Forth Worth, TX) internal limiting membrane (ILM) forceps compared with conventional (Grieshaber; Alcon) ILM forceps for peeling of the ILM. METHODS: Patients were prospectively assigned in a 1:1 randomized fashion to undergo ILM peeling using microserrated forceps or conventional forceps. Rates of retinal hemorrhages, deep retinal grasps, ILM regrasping, time to ILM removal, and surgeon questionnaire comparing the use of microserrated and conventional ILM forceps were analyzed. RESULTS: A total of 90 eyes of 90 patients were included in this study. The mean number of deep retinal grasps was higher in the conventional forceps group (1.51 ± 1.70 vs. 0.33 ± 0.56, respectively [P < 0.0001]). The mean number of failed ILM grasps was higher with conventional forceps (6.62 ± 3.51 vs. 5.18 ± 2.06 [P = 0.019]). Microserrated forceps provided more comfortability (lower number) in initiating the ILM flap (2.16 ± 0.85 vs. 1.56 ± 0.76, P < 0.001), comfortability in regrasping the ILM flap (2.51 ± 1.01 vs. 1.98 ± 0.89, P = 0.01), and comfortability in completing the ILM flap (2.42 ± 1.03 vs. 1.84 ± 1.02, P = 0.01). CONCLUSION: Surgeons utilizing the microserrated forceps experienced fewer deep retina grasps and fewer failed ILM grasps compared with conventional ILM forceps. The microserrated forceps was also a more favorable experience subjectively among the surgeons.

OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

Patient Accessibility to Eye Care in the United States.

PURPOSE: The United States (US) federal government uses health provider shortage areas (HPSAs) to define patient accessibility to primary care physicians. It is unclear whether HPSAs can be applied to eye care providers (ECPs). Our study determined the applicability of federal HPSA designations to ECP availability in the US. DESIGN: Cross-sectional study. PARTICIPANTS: US general population and ophthalmologists/optometrists in the Medicare database. METHODS: The primary care HPSA score, visual impairment prevalence, and ECP location were determined for each census tract or county using data from the US Department of Health and Human Services, the Centers for Disease Control and Prevention, and Centers for Medicare and Medicaid Services. MAIN OUTCOME MEASURES: Association of HPSA with vision loss and ECP density was examined. The 2-step floating catchment area approach was used to newly define eye care shortage areas (patient accessibility score [PAS], higher being worse accessibility) for every county in the US, by weighting the 2-step FCA scores by prevalence of vision loss and ECP density. Multivariable logistic regression was used to identify sociodemographic variables associated with areas of ECP shortage. RESULTS: Among 72 735 census tracts included, statistically significant but weak correlations of HPSA score with visual impairment (VI) (r = 0.38; P < 0.0001) and ECP density per county population (r = -0.18; P < 0.0001) were found. Only 54.0% of census tracts with < 25th percentile ECP density per county were HPSAs (P < 0.0001). Of census tracts > than 75th percentile for VI only 58.0% were HPSAs (P < 0.0001). Multivariable regression found a higher odds of ECP PAS ≥ 75th percentile (worse accessibility) in rural counties (adjusted odds ratio [aOR], 2.47; 95% confidence interval [CI], 1.93-3.67; P < 0.001) and counties with a greater prevalence of residents with less than a high school education (aOR, 1.21; 95% CI, 1.19-1.25; P < 0.001), residents ≥ 65 years of age (aOR, 1.10; 95% CI, 1.07-1.13; P < 0.001), and uninsured residents (aOR, 1.04; 95% CI, 1.01-1.06; P < 0.001). Counties with a greater proportion of men (aOR, 0.93; 95% CI, 0.89-0.967; P < 0.001) or White residents (aOR, 0.99; 95% CI, 0.98-0.99) had a lower odds of ECP PAS ≥ 75th percentile. CONCLUSIONS: Current HPSAs only weakly correlate with ECP supply. We propose a new approach to identify counties with high need but limited access to eye care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Indications for surgical management of retained lens fragments.

PURPOSE OF REVIEW: Retained lens fragments are a relatively rare occurrence after cataract surgery. While no definite guidelines for the surgical management or timing of surgery of this complication exist, surgery is indicated for patients with large lens fragments, persistent inflammation, secondary glaucoma, corneal edema, retinal tears or detachments, and associated endophthalmitis. The aim of this review is to summarize the current surgical management of retained lens material. RECENT FINDINGS: The Intelligent Research in Sight registry database of 2.26 million patients who underwent cataract surgery in the US indicated that 0.18% (1 in 563) had secondary removal of retained lens fragments in the anterior chamber in the operating room within 1 year of the original cataract surgery. The risk of returning to the operating room for retained lens material removal was greater among men, smokers, patients with Medicaid or military insurance, and those who had complex cataract surgery. Medical management with topical corticosteroids or observation may be considered for small lens fragments, but surgical removal remains the mainstay of the treatment for large lens fragments. SUMMARY: Retained lens fragments following cataract surgery may result in various vision-threatening complications. Understanding the risk factors, diagnosis, and surgical management of retained lens fragments are critical to preserving good visual outcomes. Vitrectomy is effective in patients with posterior nuclear fragments, retinal detachment, endophthalmitis, or uncontrolled glaucoma not responding to medical management. The best timing for surgery for retained lens fragments should be further investigated in a prospective study.

REGIONAL POPULATION MOBILITY AND OUTPATIENT RETINA VISITS IN THE UNITED STATES DURING THE COVID-19 PANDEMIC.

PURPOSE: To characterize how community mobility patterns across the United States correlate with local changes in retina visits during the pandemic. METHODS: Outpatient retina clinic visits were linked to population mobility by combining multiple public data sets, including the Google Community Mobility Reports and data from the Centers for Disease Control and Infection. Percentage change from baseline in daily-average number of retina visits by county and mobility were measured by county. RESULTS: A total of 2,159,689 patient visits were examined across 332 counties. Daily-average retina visits decreased by 7.0%, 19.0%, 5.0%, and 4.0% from Quarter 1 to 4 of 2020. This decrease was negatively correlated with increased incident of COVID-19 deaths for Quarters 1 to 3 (r = -0.13, r = -0.16, and r = -0.15, respectively, P < 0.001) and increased incident cases for Quarters 1 and 2 (r = -0.18, r = -0.13, respectively, P < 0.001). Daily-average retina visits relative to baseline were significantly lower for metropolitan counties in Quarters 1 and 2, compared with urban and rural (P < 0.001). The decline in retina visits had greatest association with decline in workplace visits in Quarters 1 to 3 (r = 0.27, r = 0.09, r = 0.12, respectively, P < 0.001 for all). CONCLUSION: This study provides insight into how regional mobility patterns may help to explain and predict patient behaviors and retina outpatient visit responses during the COVID-19 pandemic.

CLINICAL OUTCOMES OF PATIENTS WITH ENDOPHTHALMITIS AFTER DEXAMETHASONE INTRAVITREAL IMPLANT.

PURPOSE: To report a case series of endophthalmitis associated with intravitreal dexamethasone injections in a single practice and to discuss the clinical findings and visual outcomes of each case. METHODS: All endophthalmitis cases following intravitreal dexamethasone injections performed from January 1, 2014 to October 20, 2020 were identified using Wills Eye/MidAtlantic billing records. The diagnosis, clinical information, and microbiology were confirmed for each case. Data were analyzed using Excel (Microsoft Excel, Redmond, WA). RESULTS: Four cases of endophthalmitis were identified from 3,925 intravitreal dexamethasone injections in a single practice and one case was referred from an outside institution, resulting in an incidence of 0.102% (1 in 981 injections). Mean age was 82.3 years (range, 63-88 years) with a mean of 11.3 intravitreal dexamethasone injections performed (range, 2-30 injections) before endophthalmitis. Cases presented with endophthalmitis a mean (SD) of 3.6 (1.64) days after causative injection. Three cases grew gram-positive organisms. All patients responded to intravitreal antibiotics. Mean logarithm of the minimal angle of resolution visual acuity at causative injection, endophthalmitis presentation, 3 months, and last follow-up was 0.44 (20/55), 2.22 (20/3,319), 1.18 (20/303), and 1.46 (20/577), respectively. CONCLUSION: Endophthalmitis following intravitreal steroid injections may occur more frequently than other intravitreal injections. Dexamethasone-attributed endophthalmitis remains uncommon, and prompt intravitreal antibiotic treatment seems to be effective in this series.

Emerging treatments for geographic atrophy in age-related macular degeneration.

PURPOSE OF REVIEW: This review describes therapeutic research programs for geographic atrophy (GA) due to age-related macular degeneration (AMD). We highlight clinical trial data from phase I, II, and III studies. RECENT FINDINGS: There are currently no treatments for GA, a form of advanced AMD that causes significant visual morbidity. Currently, therapeutic candidates are being developed to delay further progression of GA or even attempt to reverse some of the damage. The approaches to therapy range from molecular targets to cell transplantation. Studies of these novel treatment approaches have demonstrated varying degrees of success. The progress in understanding the disease pathophysiology as well as clinical trial data is reviewed. SUMMARY: There are promising new treatments to prevent GA progression as well as some that may reverse the disease course.

THE RELATIONSHIP BETWEEN STOPPER POSITION AND INJECTION VOLUME IN RANIBIZUMAB AND AFLIBERCEPT PREFILLED SYRINGES.

PURPOSE: To determine the relationship between stopper position and injection volume in aflibercept and ranibizumab prefilled syringes (PFS). METHODS: Empty aflibercept 2.0 mg PFS and ranibizumab 0.3 mg and 0.5 mg PFS were collected and refilled with saline. The stopper was positioned relative to the preprinted mark, and resulting injection volumes were recorded. The position for double the on-label volume was confirmed with repeated testing. The quantitative relationship between position and volume was calculated. RESULTS: In ranibizumab PFS, doubling the distance increased the volume injected by 2.6 times. Positioning the stopper 4.0, 3.0, 2.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.13, 0.1, 0.08, 0.05, and 0.03 mL, respectively. The relationship between position (x) and volume (y) was y = 0.019x + 0.048. In aflibercept PFS, doubling the distance increased the volume injected by 3.2 times. Positioning the stopper 2.5, 2.0, 1.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.16, 0.14, 0.11, 0.05, and 0.02 mL, respectively. The relationship between position (x) and volume (y) was y = 0.041x + 0.059. CONCLUSION: Proper positioning of the stopper at the preprinted mark accurately delivers the on-label volume with both the ranibizumab and aflibercept PFS. However, small variations in stopper position appear to have substantial effects on the volume of drug injected.

GEOGRAPHIC ACCESS DISPARITIES TO CLINICAL TRIALS IN RETINOPATHY OF PREMATURITY IN THE UNITED STATES.

BACKGROUND/PURPOSE: To identify geographic and socioeconomic variables predictive of residential proximity to retinopathy of prematurity (ROP) clinical trial locations. METHODS: This cross-sectional epidemiological study used census tract-level data from three national public data sets and trial-level data from ClinicalTrials.gov. Socioeconomic predictors of driving distance and time to the nearest ROP clinical trial location were identified. Primary outcomes were time >60 minutes and distance >60 miles traveled to the nearest ROP clinical trial site. RESULTS: Multivariate analysis showed that residents were more likely to travel >60 minutes to the nearest ROP clinical trial site if they lived in census tracts that were rural (adjusted odds ratio 1.20, P = 0.0002), had higher percentages of the population living ≤ federal poverty level (fourth quartile vs. first quartile, adjusted odds ratio 1.19, P < 0.0001), or had less education (associate vs. bachelor's degree, adjusted odds ratio 1.01, P <0.007). By contrast, counties with higher percentages of births with birth weight <1500 g (adjusted odds ratio 0.88, P = 0.0062) were less likely to travel >60 minutes. Similar variables predicted travel distance. CONCLUSION: Although counties with higher incidences of very low-birth-weight infants were closer to ROP clinical trial sites, residents living in rural and low-income census tracts had significantly greater travel burdens.

PATIENTS PRESENTING EMERGENTLY WITH PROLIFERATIVE DIABETIC RETINOPATHY: Follow-up and Factors Associated With Compliance.

PURPOSE: To determine the rate of follow-up after emergent encounters for proliferative diabetic retinopathy and to identify patient or visit characteristics associated with follow-up compliance. METHODS: A retrospective cohort study of patients presenting to an ophthalmic emergency department with active proliferative diabetic retinopathy between May 2014 and December 2016 was conducted. Demographic data and encounter data were gathered for each emergency department visit. Compliance with follow-up was defined as a completed clinic visit as scheduled after the emergency encounter. RESULTS: A total of 590 emergency department encounters were included. The overall follow-up rate was 61.9%. Married patients and those with Public Health Trust insurance had increased odds of compliance (odds ratio [OR]: 1.507, P = 0.04; OR: 2.749, P < 0.0001). Patients with Medicaid had reduced odds (OR: 0.543, P = 0.004). Patients with longer emergency department encounters and longer intervals to follow-up had reduced odds (OR: 0.948, P = 0.001; OR of 0.941, P < 0.0001). The other characteristics were not significantly associated with follow-up compliance. CONCLUSION: Patients who present emergently with active proliferative diabetic retinopathy are at high risk of following up noncompliance. Characteristics with significant effects on the odds of follow-up compliance include specific insurance payer, marriage status, length of visit, and interval to follow-up.

Outcomes of Eyes Lost to Follow-up After Treatment With Intraocular or Periocular Steroid Injections.

Purpose: To evaluate the visual, intraocular pressure (IOP), and anatomic outcomes of eyes with loss to follow-up (LTFU) after intravitreal or periocular steroid injections. Methods: Patients receiving intraocular or periocular steroid injections and with LTFU for at least 180 days were included in this retrospective cohort study. Charts were reviewed for the visual acuity (VA), IOP, and central foveal thickness at the visit before LTFU, the first return visit, and 3, 6, and 12 months after return. Results: Fifty-three eyes of 47 patients were identified. The mean (±SD) age was 62.3 ± 14.9 years, the mean LTFU time was 295 ± 181.2 days (range, 182-1101), and the mean follow-up after return was 354 ± 339.3 days (range, 32-1141). The overall mean number of steroid injections was 5.2 ± 3.9 (range, 1-18). Compared with the mean logMAR VA at the visit before LTFU (0.59 [Snellen 20/77]), the mean VA remained stable at all timepoints after return as follows: return visit (0.62 [20/83]; P = .6), month 3 (0.55 [20/70]; P = .6), month 6 (0.55 [20/70]; P = .5), month 12 (0.64 [20/87]; P = .6), and final visit (0.69 [20/97]; P = .2). At the first return visit, 8 (15%) of 53 patients had an IOP of 21 mm Hg or higher (range, 21-31); 2 required treatment with a new antihypertensive medication (latanoprost and timolol, respectively). Conclusions: Patients with LTFU after receiving steroid injections maintained their VA. No patient required incisional glaucoma surgery. Compared with other etiologies, eyes with diabetic macular edema had a greater increase in IOP.

A PCR-Based Survey of Methane-Cycling Archaea in Methane-Soaked Subsurface Sediments of Guaymas Basin, Gulf of California.

The Guaymas Basin in the Gulf of California is characterized by active seafloor spreading, the rapid deposition of organic-rich sediments, steep geothermal gradients, and abundant methane of mixed thermogenic and microbial origin. Subsurface sediment samples from eight drilling sites with distinct geochemical and thermal profiles were selected for DNA extraction and PCR amplification to explore the diversity of methane-cycling archaea in the Guaymas Basin subsurface. We performed PCR amplifications with general (mcrIRD), and ANME-1 specific primers that target the alpha (α) subunit of methyl coenzyme M reductase (mcrA). Diverse ANME-1 lineages associated with anaerobic methane oxidation were detected in seven out of the eight drilling sites, preferentially around the methane-sulfate interface, and in several cases, showed preferences for specific sampling sites. Phylogenetically, most ANME-1 sequences from the Guaymas Basin subsurface were related to marine mud volcanoes, seep sites, and the shallow marine subsurface. The most frequently recovered methanogenic phylotypes were closely affiliated with the hyperthermophilic Methanocaldococcaceae, and found at the hydrothermally influenced Ringvent site. The coolest drilling site, in the northern axial trough of Guaymas Basin, yielded the greatest diversity in methanogen lineages. Our survey indicates the potential for extensive microbial methane cycling within subsurface sediments of Guaymas Basin.

Seasonal and Environmental Variations in Endophthalmitis after Intravitreal Anti-vascular Endothelial Growth Factor Injection: A Six-year Review.

PURPOSE: To evaluate seasonal and environmental variations on the incidence and outcomes of postinjection endophthalmitis. METHODS: A single-center, retrospective cohort study was conducted including all patients diagnosed with post-injection endophthalmitis between 2013-2018. Associations between climate variables and endophthalmitis incidence were evaluated. RESULTS: Of 423,297 injections administered, seasonal distribution in spring, summer, autumn, and winter was 26%, 27%, 25%, and 22%, respectively. Of 171 cases of endophthalmitis identified, seasonal distribution over the spring, summer, autumn, and fall was 25%, 23%, 26%, and 26%, respectively. Endophthalmitis incidence was not correlated with monthly precipitation (p = 0.45), monthly snowfall (p = 0.49), or monthly temperature (p = 0.65). Worse visual outcomes at initial endophthalmitis presentation were correlated with increased precipitation level (p = 0.025) but were not correlated with snowfall level (p = 0.228) or mean monthly temperature (p = 0.132). Although there were no seasonal variations of visual acuity at endophthalmitis presentation (p = 0.894), odds of final visual acuity returning to within two lines of pre-endophthalmitis visual acuity were worse among patients with endophthalmitis diagnosed in the spring (OR, 0.041; p = 0.016). CONCLUSION: In contrast to previous work on postcataract endophthalmitis, seasonal and weather factors were not associated with post-injection endophthalmitis risk or bacterial species isolated. Visual outcomes at initial endophthalmitis presentation were correlated with precipitation, and worse visual outcomes were seen in patients who developed endophthalmitis in the spring.

Epiretinal Membrane Surgery after Retinal Detachment Repair: Visual Acuity Outcomes and OCT Analysis.

PURPOSE: To assess visual acuity (VA) outcomes of epiretinal membrane (ERM) surgery following primary rhegmatogenous retinal detachment (RD) repair and to identify OCT features predictive of visual outcomes. DESIGN: Retrospective, consecutive case series. SUBJECTS: Eyes undergoing pars plana vitrectomy (PPV) with membrane peel (MP) surgery for ERM following primary RD repair (PPV with or without scleral buckle (SB) and gas tamponade). METHODS: Retrospective chart review from 2015 to 2018. A previously described ERM grading scale was utilized for OCT structural analysis. MAIN OUTCOME MEASURES: Visual acuity (VA) and change in VA from pre- MP to 6 months and final follow-up. Secondary outcomes included RD and OCT features predictive of VA, as well as RD factors associated with need for subsequent MP surgery. RESULTS: 53 eyes of 53 patients underwent MP following RD repair. VA improved significantly from logMAR 1.00 ± 0.51 (Snellen 20/200) pre-MP to 0.45 ± 0.41 (20/56) at 6 months and 0.42 ± 0.41 (20/53) at final follow-up, (p<0.001) for each respectively. Macula on eyes had better 6 month [0.29 ± 0.18 (20/39) vs. 0.51 ± 0.46 (20/65), p=0.02] and final VA [0.29 ± 0.14 (20/39) vs. 0.46 ± 0.47 (20/58), p=0.04] after MP surgery. VA improved significantly from pre-MP to 6 months and final follow-up regardless of macula status. MP occurring ≤180 days from RD repair and IS/OS loss were associated with worse pre-MP VA [1.13 ± 0.09 (20/270) vs. 0.82 ± 0.07(20/132), p=0.01 and 1.21 ± 0.07 (20/324) vs. 0.74 ± 0.09 (20/110) p=0.0003, respectively]. IS/OS loss [adjusted means 0.54 ± 0.07 (20/69) vs. 0.25 ± 0.08 (20/36) at final visit, p=0.006] and RD repair with PPV/SB [0.53 ± 0.08 (20/68) vs. 0.31 ±0.07 (20/41) at final visit, p=0.03] were significantly associated with worse VA at both 6 months and final follow-up. CONCLUSIONS: Eyes undergoing MP after RD repair have significant visual acuity gains independent of macula-status at time of RD repair. Pre-operative IS/OS disruption was the OCT feature best predictive of visual acuity.

Endophthalmitis After Intravitreal Anti-Vascular Endothelial Factor Injections: Outcomes of Eyes Managed Without Microbiologic Cultures.

PURPOSE: To evaluate outcomes of eyes that developed endophthalmitis after intravitreal anti-vascular endothelial growth factor injections that were managed without microbiologic cultures. DESIGN: Retrospective, single-center, comparative cohort study. METHODS: We included all eyes with postinjection endophthalmitis from July 1, 2013, to September 1, 2019. Endophthalmitis cases were divided into the culture group if treated with intravitreal antibiotics and a vitreous or aqueous tap sent for microbiologic sampling or into the no culture group if treated with immediate injection of intravitreal antibiotics with an anterior chamber paracentesis that was not sent for microbiologic sampling. The main outcome measures were visual acuity, the incidence of retinal detachment, and the need for additional procedures. RESULTS: Of 165 endophthalmitis cases identified, 119 (72%) were in the culture group and 46 (28%) were in the no culture group. At endophthalmitis presentation, eyes in the culture group had a mean logMAR VA of 1.98 (∼20/1900) compared with 1.90 (∼20/1600) for eyes in the no culture group (P = .589). At the 6-month follow-up, the mean vision loss was 5.5 lines lost from baseline for the culture group compared with 2.5 lines lost for the no culture group (P = .017). Eyes in the culture group required a subsequent pars plana vitrectomy in 29 of 119 cases (24%) compared with 7 of 46 cases (15%) in the no culture group (P = .29). Six of 119 eyes (5%) in the culture group developed secondary retinal detachments compared with none in the no culture group (P = .143). CONCLUSIONS: When access to microbiologic facility is not available, the management of postinjection endophthalmitis using intravitreal antibiotics without microbiologic cultures may be an acceptable treatment strategy.

Cell-based therapies for retinal diseases: a review of clinical trials and direct to consumer "cell therapy" clinics.

BACKGROUND: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside of legitimate studies are presented. MAIN BODY: Cell-based therapies can be applied to disorders that involve the RPE via a variety of techniques. A defining characteristic of any cell therapy treatment is the cell source used: human embryonic stem cells, induced pluripotent stem cells, and human umbilical tissue-derived cells have all been studied in published trials. In addition to the cell source, various trials have evaluated particular immunosuppression regiments, surgical approaches, and outcome measures. Data from early phase studies investigating cell-based therapies in non-neovascular age-related macular degeneration (70 patients, five trials), neovascular age-related macular degeneration (12 patients, four trials), and Stargardt's macular dystrophy (23 patients, three trials) have demonstrated safety related to the cell therapies, though evidence of significant efficacy has not been reported. This is in contrast to the multiple reports of serious complications and permanent vision loss in patients treated at "cell therapy" clinics. These interventions are marketed directly to patients, funded by the patient, lack Food and Drug Administration approval, and lack significant oversight. CONCLUSION: Currently, there are no proven effective cell-based treatments for retinal diseases, although several trials have investigated potential therapies. These studies reported favorable safety profiles with multiple surgical approaches, with cells derived from multiple sources, and with utilized different immunosuppressive regiments. However, data demonstrating the efficacy and long-term safety are still pending. Nevertheless, "cell therapy" clinics continue to conduct direct-to consumer marketing for non-FDA-approved treatments with potentially blinding complications.

Anti-Vascular Endothelial Growth Factor and Panretinal Photocoagulation Use after Protocol S for Proliferative Diabetic Retinopathy.

PURPOSE: To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S. DESIGN: A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). PARTICIPANTS: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents. METHODS: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015). MAIN OUTCOME MEASURES: Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR. RESULTS: From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n = 6379) were anti-VEGF agents, and 36.4% (n = 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: ß = -32 vs. post-Protocol S: -77; P = 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (ß = -48 vs. 161, respectively; P = 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (ß = -9 vs. -58 respectively; P = 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (ß = -57 vs. 187; P = 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (ß = -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (ß = -48 vs. 140, respectively; P < 0.001). CONCLUSIONS: Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.

Artificial intelligence in global ophthalmology: using machine learning to improve cataract surgery outcomes at Ethiopian outreaches.

Differences between target and implanted intraocular lens (IOL) power in Ethiopian cataract outreach campaigns were evaluated, and machine learning (ML) was applied to optimize the IOL inventory and minimize avoidable refractive error. Patients from Ethiopian cataract campaigns with available target and implanted IOL records were identified, and the diopter difference between the two was measured. Gradient descent (an ML algorithm) was used to generate an optimal IOL inventory, and we measured the models performance across varying surplus levels. Only 45.6% of patients received their target IOL power and 23.6% received underpowered IOLs with current inventory (50% surplus). The ML-generated IOL inventory ensured that more than 99.5% of patients received their target IOL when using only 39% IOL surplus. In Ethiopian cataract campaigns, most patients have avoidable postoperative refractive error secondary to suboptimal IOL inventory. Optimizing the IOL inventory using this ML model might eliminate refractive error from insufficient inventory and reduce costs.

Geographic Access Disparities of Clinical Trials in Neovascular Age-Related Macular Degeneration in the United States.

To identify geographic and socioeconomic variables predictive of residential proximity to neovascular age-related macular degeneration (nAMD) clinical trial locations. DESIGN: Retrospective, cross-sectional study. METHODS: Census tract-level data from public datasets and trial-level data from ClinicalTrials.gov were analyzed. We calculated the driving distance (>60 miles) and time (>60 minutes) from the population-weighted US census tract centroid to the nearest clinical trial site. RESULTS: We identified 42 trials studying nAMD across 829 unique clinical trial sites in the United States. In a multivariable model, driving distance >60 miles had a significant association with rural location (adjusted odds ratio [aOR] 5.54; 95% confidence interval [CI] 3.86-7.96, P < .0001) and with Midwest (aOR 2.30; 95% CI 1.21-4.38, P = .01) and South (aOR 2.43; 95% CI 1.21-4.91, P = .01) as compared to the Northeast region, and with some college or an associate's degree, as compared to a bachelor's degree (aOR 1.02; 95% CI 1.01-1.04, P = .0007, and aOR 1.05; 95% CI 1.00-1.10, P = .04, respectively). Lower odds of traveling >60 miles to the nearest nAMD trial site were associated with census tracts with a higher percentage of blacks (aOR 0.98; 95% CI 0.97-0.99, P < .0001), Hispanics (aOR 0.97; 95% CI 0.95-0.99, P = .002), and Asians (aOR 0.90; 95% CI 0.88-0.93, P < .0001), as compared to whites, and with a lower percentage of the population <200% of the federal poverty level. Similar predictors were found in time traveled >60 minutes. CONCLUSIONS: There are geographic access disparities of clinical trial sites for nAMD in the United States.