Impact of Patient Race/Ethnicity on Premium Intraocular Lens Utilization.

OBJECTIVE: To evaluate the relationship between social determinants of health and the likelihood of receiving a premium intraocular lens (IOL) at the time of cataract surgery. METHODS: Retrospective chart review of a single-center, academic ophthalmology practice over a one-year period, with a primary outcome measure of placement of either a premium or standard IOL. We used logistic regression to calculate the odds of receiving a premium IOL, stratifying patients based on self-identified race/ethnicity, age, sex, insurance type (private insurance vs. Medicare or Medicaid), estimated household income (based on median household income for zip code), and presence of ocular pathology. RESULTS: Compared with self-identified White patients, Black patients were least likely to receive premium IOLs (OR=0.220, 95% CI 0.137-0.340, P<0.001), followed by Hispanic patients (OR=0.308, 95% CI 0.104-0.730) and Asian patients (OR=0.479, 95% CI 0.302-0.734). Patients with Medicare or Medicaid insurance were also less likely to receive premium IOLs (OR 0.522, 95% CI 0.336-0.784). CONCLUSIONS: White patients in our practice were more likely to receive premium IOLs than non-White patients, even when controlling for age, sex, insurance type, estimated median household income, and presence of ocular comorbidities. The underlying reason for this disparity should be explored further.

Tandem Mass Tag LC-MS/MS of Aqueous Humor From Individuals With Type 2 Diabetes Without Retinopathy Reveals Early Dysregulation of Synaptic Proteins.

Purpose: An early neurodegenerative component of diabetic retinal disease (DRD) that precedes the vascular findings of clinically diagnosed diabetic retinopathy (DR) is increasingly being recognized. However, the relevant molecular mechanisms and biomarkers for early DRD are poorly defined. The purpose of this study was to uncover novel potential mediators of early diabetic retinal neuronal dysfunction through analysis of the aqueous fluid proteome in preclinical DR. Methods: Aqueous fluid was collected from subjects with type 2 diabetes mellitus (DM) but no clinical DR and from nondiabetic controls undergoing routine cataract surgery. Preoperative spectral-domain optical coherence tomography of the macula was obtained. Tandem mass tag LC-MS/MS was performed to identify proteins differentially present in diabetic and control aqueous fluid, and proteins with >50% change and P < 0.05 were considered significant. Selected results were validated with western blot of human aqueous fluid samples. Results: We identified decreased levels of proteins implicated in neuronal synapse formation and increased levels of inflammatory proteins in the aqueous fluid from patients with type 2 DM but no DR compared with controls. Of the differentially present synaptic proteins that we identified and confirmed with western blot, the majority have not previously been linked with DRD. Conclusions: The proteomic profile of aqueous fluid from individuals with type 2 DM but no DR suggests that retinal neuronal dysfunction and inflammation represent very early events in the pathophysiology of DRD. These findings support the concept that diabetic retinal neurodegeneration precedes vascular pathology and reveal novel potential mediators and/or biomarkers warranting further investigation.

Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is the first randomized clinical trial to study the efficacy of long-term (1 year) suppressive valacyclovir treatment on herpes zoster ophthalmicus (HZO) outcomes. This article details the baseline characteristics of participants. SETTING: The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. STUDY POPULATION: Immunocompetent adults with a history of a characteristic HZO unilateral rash and documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, or iritis within the preceding year, enrolled in ZEDS from November 2017 to January 2023. INTERVENTION: Participants were randomized to double-masked oral valacyclovir 1 gm daily versus placebo for 1 year of treatment and followed for 18 months. RESULTS: Five hundred twenty-seven participants were enrolled across 4 strata according to age at HZO onset (younger or older than 60 years) and duration of HZO at enrollment (less or greater than 6 months), with an even distribution of men and women and a median age of 60 years. More participants with recent (57%, 300/527) than chronic HZO and younger than 60 years at HZO onset (54%, 286/527) were enrolled. Most participants were treated acutely with a recommended antiviral regimen (91%, 480/527) and had not been vaccinated against zoster (79%, 418/527). CONCLUSIONS: The broad ZEDS study population enhances the likelihood that ZEDS will provide generalizable high-quality evidence regarding the efficacy and safety of suppressive valacyclovir for HZO immunocompetent adults and whether it should become standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03134196.

Anti-inflammatory medication use after cataract surgery: online survey of practice patterns.

PURPOSE: To determine current prescribing patterns for topical or intraocular/periocular anti-inflammatory medications (AIMs) after routine cataract surgery. SETTING: kera-net online members. DESIGN: Cross-sectional survey. METHODS: An online survey was distributed to subscribers of kera-net, a global online platform sponsored by the Cornea Society. Questions were asked regarding the use of topical or intraocular/periocular AIM after cataract surgery and types of medications prescribed. RESULTS: Of 217 surgeon respondents (23% response rate), 171 (79%) practiced in the United States and 171 (79%) were cornea subspecialists. Most of the respondents (n = 196, 97%) prescribed topical corticosteroids after routine cataract surgery. The most frequently prescribed were prednisolone acetate (n = 162, 83%), followed by dexamethasone (n = 26, 13%), difluprednate (n = 24, 12%), and loteprednol etabonate (n = 13, 7%). Corticosteroids comprised (n = 40, 32%) of total intraocular/periocular injections, with triamcinolone acetonide 10 or 40 mg (n = 19, 47.5%) most commonly used. 23 surgeons (58%) who utilized intraocular/periocular corticosteroids also prescribed topical corticosteroids. Topical nonsteroidal anti-inflammatory drugs were prescribed postoperatively by 148 surgeons (73%). CONCLUSIONS: Most surgeons prescribed topical AIM after routine cataract surgery. Many surgeons injected intraocular or periocular AIM while prescribing topical AIM. The diversity of practice patterns may reflect the lack of clear evidence-based guidelines.

Accuracy of intraocular lens formulas in combined phacovitrectomy.

PURPOSE: To assess the refractive accuracy of eight intraocular lens (IOL) formulas in eyes that underwent combined phacovitrectomy. METHODS: A retrospective chart review of 59 eyes that underwent uncomplicated phacovitrectomy between 2017 and 2020 at the Johns Hopkins Wilmer Eye Institute. Inclusion criteria were postoperative best corrected visual acuity of 20/40 or better within 6 months of surgery and IOL implantation in the capsular bag. The Barrett Universal II (BUII), Emmetropia Verifying Optical (EVOv2.0), Hill-Radial Basis Function (Hill-RBFv3.0), Hoffer Q, Holladay I, Kane, Ladas Super Formula (LSF), and SRK/T formulas were compared for accuracy in predicting postoperative spherical equivalents (SE) using Wilcoxon rank sum tests. Pearson's correlation coefficients were used to assess correlations between biometric parameters and errors for all formulas. RESULTS: Prediction errors of SE ranged from - 1.69 to 1.43 diopters (D), mean absolute errors (MAE) ranged from 0.39 to 0.47 D, and median absolute errors (MedAE) ranged from 0.23 to 0.37 D among all formulas. The BUII had the lowest mean error (- 0.043), MAE (0.39) and MedAE (0.23). The BUII also had the highest percentage of eyes with predicted error within ± 0.25 D (51%) and ± 0.50 D (83%). Based on MedAE however, no pairwise comparisons resulted in statistically significant differences. Axial length (AL) was positively correlated with the error from the Hoffer Q and Holladay I formulas (correlation coefficients = 0.34, 0.30, p values < 0.01, 0.02 respectively). CONCLUSION: While all eight IOL formulas had comparable accuracy in predicting refractive outcomes in eyes undergoing combined phacovitrectomy, the BUII and Kane formulas had a tendency to greater accuracy.

Early Endophthalmitis Rates and Risk Factors After Corneal Transplant Surgeries in Medicare Beneficiaries From 2016 to 2019.

PURPOSE: The aims of this study were to determine rates of early postkeratoplasty endophthalmitis and identify sociodemographic and medical risk factors in the Medicare population. METHODS: Using a retrospective cohort design, patients aged 65 years and older undergoing penetrating keratoplasty (PK), endothelial keratoplasty (EK), and anterior lamellar keratoplasty (ALK) from 2016 to 2019 among 100% Medicare Fee-or-Service database were included. Rates of early endophthalmitis within 42 days of keratoplasty were determined using the International Classification of Diseases, 10th Revision-Clinical Modification diagnostic codes. Patient and physician characteristics were compared using x2 tests, and a multivariable logistic regression model was used to evaluate factors associated with endophthalmitis. RESULTS: The overall early endophthalmitis rate after keratoplasty was 0.39% (n = 216/54,822) with a median time to diagnosis of 14 (interquartile range: 5-25) days. Rates by keratoplasty types were 1.31% for cataract surgery combined with PK, 1.13% for PK, and 0.22% for EK. On multivariable analysis, the odds of endophthalmitis were higher for PK [odds ratio (OR): 5.46, 95% confidence interval (CI), 3.98-7.49] and ALK (OR: 5.45, 95% CI, 2.59-11.49) relative to EK. Patients with a Charlson Comorbidity Index (CCI) ≥3 had higher odds of endophthalmitis (OR: 1.82; 95% CI, 1.28-2.58) relative to patients with a CCI of 0. Practices located in the Midwest (OR: 0.59, 95% CI, 0.36-0.96), West (OR 0.57; 95% CI, 0.35-0.93), and Northeast (OR: 0.59 95% CI, 0.35-0.99) had lower odds of reporting endophthalmitis when compared to the South. CONCLUSIONS: Patients undergoing PK and ALK and those with a CCI ≥3 had higher odds of endophthalmitis relative to EK and patients without comorbidities, respectively. Practices in the West, Midwest, and Northeast had lower odds of endophthalmitis relative to the South.

Patient Utilization of Premium Intraocular Lenses Before and During the COVID-19 Pandemic.

PURPOSE: To compare the choice of intraocular lens (IOL) and sociodemographic characteristics between patients who underwent elective cataract surgery before the COVID-19 pandemic and during the pandemic at the Wilmer Eye Institute. METHODS: A retrospective chart review of patients who underwent cataract surgery before the COVID-19 pandemic (June 1 to November 30, 2019) and during the pandemic (June 1 to November 30, 2020) was conducted. Sociodemographic information, including age, sex, race, and insurance, and choice of IOL (premium or standard) were analyzed. The association between timing of surgery and choice of IOL was analyzed using multivariable logistic regression. RESULTS: The study included 2,877 patients (3,946 eyes) before COVID-19 and 2,564 patients (3,605 eyes) during COVID-19. However, 9.0% (357/3,946) of surgeries before COVID-19 used premium IOLs compared with 11.1% (399/3,605) during COVID-19 ( P =0.004). There was no difference in the racial characteristics of patients between before and during COVID-19. After adjusting for time of surgery and demographics, the odds of choosing premium IOLs for black patients was 0.32 times the odds for white patients ( P <0.001). There was an increase in private-insured patients but a decrease in Medicare-insured patients during COVID-19. After adjusting for time of surgery and demographics, private-insured patients had higher odds of choosing premium IOLs ( P <0.001), whereas Medicaid-insured patients had lower odds ( P =0.007) when compared with Medicare-insured patients. CONCLUSION: More patients chose premium IOLs during COVID-19 than before COVID-19, concurrent with change in insurance status. White patients were more likely to choose premium IOLs than black patients, as were private-insured patients compared with Medicare-insured patients.

How Ophthalmologists Can Decarbonize Eye Care: A Review of Existing Sustainability Strategies and Steps Ophthalmologists Can Take.

TOPIC: Understanding approaches to sustainability in cataract surgery and their risks and benefits. CLINICAL RELEVANCE: In the United States, health care is responsible for approximately 8.5% of greenhouse gas (GHG), and cataract surgery is one of the most commonly performed surgical procedures. Ophthalmologists can contribute to reducing GHG emissions, which lead to a steadily increasing list of health concerns ranging from trauma to food instability. METHODS: We conducted a literature review to identify the benefits and risks of sustainability interventions. We then organized these interventions into a decision tree for use by individual surgeons. RESULTS: Identified sustainability interventions fall into the domains of advocacy and education, pharmaceuticals, process, and supplies and waste. Existing literature shows certain interventions may be safe, cost-effective, and environmentally friendly. These include dispensing medications at home to patients after surgery, multi-dosing appropriate medications, training staff to properly sort medical waste, reducing the number of supplies used during surgery, and implementing immediate sequential bilateral cataract surgery where clinically appropriate. The literature was lacking on the benefits or risks for some interventions, such as switching specific single-use supplies to reusables or implementing a hub-and-spoke-style operating room setup. Many of the advocacy and education interventions have inadequate literature specific to ophthalmology but are likely to have minimal risks. CONCLUSIONS: Ophthalmologists can engage in a variety of safe and effective approaches to reduce or eliminate dangerous GHG emissions associated with cataract surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Predictors of Receiving Keratoplasty for Fuchs' Endothelial Corneal Dystrophy among Medicare Beneficiaries.

PURPOSE: To identify factors associated with receipt of endothelial keratoplasty (EK) and penetrating keratoplasty (PK) in patients with Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare beneficiaries 65 years of age or older with a FECD diagnosis between 2011 and 2019. METHODS: The 100% Medicare fee-for-service administrative claims database was queried for treatment-naïve FECD patients. A multivariate logistic regression model including age, race and ethnicity, sex, geography, ocular comorbidities and surgeries, Charlson comorbidity index (CCI), and socioeconomic status was used to identify factors associated with receipt of EK and PK. Kaplan-Meier survival analyses were used to determine the rate of EK after cataract or complex or other anterior segment surgery. MAIN OUTCOME MEASURES: Factors associated with receipt of an EK or PK, plus rate of EK after cataract or complex or other anterior segment surgery. RESULTS: Of 719 066 beneficiaries identified, 31 372 (4.4%) received an EK and 2426 (0.3%) received a PK. In a multivariate analysis, female sex decreased likelihood of both EK and PK (adjusted odds ratio 0.83 [95% confidence interval 0.81-0.85] and 0.84 [0.78-0.92], respectively), while Western residence (1.33 [1.29-1.38]; 1.25 [1.11-1.42]) compared to Southern and history of complex or other anterior segment surgery (1.62 [1.54-1.70]; 5.52 [4.97-6.12]) increased the likelihood of both. Compared to Whites, the likelihood of EK was decreased for Black (0.76 [0.72-0.80]), Asian or Pacific Islander (0.54 [0.48-0.61]), and Hispanic or Latino (0.62 [0.55-0.70]) race and ethnicity, while for the same groups likelihood of PK was increased (for Black 1.32 [1.14-1.53]; Asian/Pacific Islander 1.46 [1.13-1.89]; and Hispanic/Latino 1.62 [1.25-2.11]). Following cataract or complex/other anterior segment surgery, rates of EK were 1.3% and 3.3% at 1 year and 2.3% and 5.6% at 8 years, respectively. CONCLUSIONS: In a multivariate analysis, women beneficiaries are less likely to receive EK or PK for FECD compared with men, whereas non-White beneficiaries are less likely to receive EK and more likely to receive PK compared with White beneficiaries.

Congenital Corneal Opacity in 22q11.2 Deletion Syndrome: A Case Series.

PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes.

ABSTRACT: Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

Sex diversity within U.S. residencies: a cross-sectional study of trends from 2011 to 2019.

BACKGROUND: Despite females comprising 50.8% of the U.S. population, the percentage of females in the physician workforce is only 36.3%. Studies have examined sex trends within select specialties, however there is insufficient literature studying trends across all specialties. In this study, the authors examined trends in the proportion of female residents from 2011 to 2019 across all specialties, including both surgical and non-surgical.  METHODS: Data on the proportion of female residents from 2011 to 2019 in all specialties was extracted from the Accreditation Council for Graduate Medical Education (ACGME) Data Resource Books and analyzed with the chi-square test for trend. RESULTS: From 2011 to 2019, there was a statistically significant increase in the percentage of female residents in surgical specialties (p < 0.001) and no significant change in the percentage of female residents in non-surgical specialties. In the same time period, the specialty with the highest percentage of females was Obstetrics & Gynecology (81.3%), and the specialty with the lowest percentage of females was Orthopedic Surgery (13.8%). CONCLUSIONS: Although there has been a positive overall trend in the percentage of females entering medical and surgical specialties, the percentage of females in medicine overall still lies below that of the entire population. Increased efforts are needed to increase female representation in medicine, especially in the U.S. in specialties where they are traditionally underrepresented.

Trends, Factors, and Outcomes Associated with Immediate Sequential Bilateral Cataract Surgery among Medicare Beneficiaries.

PURPOSE: To report the incidence of immediate sequential bilateral cataract surgery (ISBCS) and delayed sequential bilateral cataract surgery (DSBCS) and to identify factors associated with undergoing ISBCS. DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare beneficiaries aged ≥ 65 who underwent ISBCS and DSBCS from 2011 through 2019. METHODS: Population-based analysis of the 100% Medicare fee-for-service carrier claims data. Logistic regression models were performed to evaluate factors associated with ISBCS. MAIN OUTCOME MEASURES: Incidence of ISBCS and DSBCS; demographic, ocular, and medical characteristics associated with receipt of ISBCS; and rates of endophthalmitis and cystoid macular edema (CME) after ISBCS or DSBCS. RESULTS: A total of 4014 (0.2%) ISBCS and 1 940 965 (99.8%) DSBCS patients were identified. Black (odds ratio [OR], 2.31; 95% confidence interval [CI], 2.06-2.59), Asian (OR, 1.82; 95% CI, 1.51-2.19), and Native American (OR, 2.42; 95% CI, 1.81-3.23) patients were more likely to receive ISBCS than White patients. Patients residing in rural areas showed a higher likelihood of ISBCS (OR, 1.26; 95% CI, 1.17-1.35) than patients in metropolitan areas. Patients undergoing surgery at a hospital, compared with an ambulatory setting (OR, 2.71; 95% CI, 2.53-2.89), were more likely to receive ISBCS. Patients with bilateral complex versus noncomplex cataract (OR, 3.23; 95% CI, 2.95-3.53) were more likely to receive ISBCS. Patients with a Charlson comorbidity index (CCI) of 1 to 2 (OR, 1.45; 95% CI, 1.29-1.62), 3 to 4 (OR, 1.70; 95% CI, 1.47-1.97), 5 to 6 (OR, 1.97; 95% CI, 1.62-2.39), and CCI ≥ 7 (OR, 1.97; 95% CI, 1.55-2.50) were more likely to receive ISBCS than those with a CCI of 0. In contrast, patients with glaucoma (OR, 0.82; 95% CI, 0.76-0.89), macular degeneration (OR, 0.75; 95% CI, 0.68-0.82), and macular hole or epiretinal membrane (OR, 0.55; 95% CI, 0.48-0.65) were less likely to undergo ISBCS than those without. Cumulatively, no significant difference was found in endophthalmitis rates within 42 days between ISBCS (1.74 per 1000 ISBCS procedures) and DSBCS (1.01 per 1000 DSBCS procedures; P = 0.15). Similarly, there was no significant cumulative difference between CME rates (P = 0.45) in ISBCS (1.79 per 100 ISBCS procedures) and DSBCS (1.96 per 100 DSBCS procedures). CONCLUSIONS: Overall use of ISBCS among Medicare beneficiaries remained low over the past decade, although rates of endophthalmitis and CME were comparable to DSBCS. Race, geography, and systemic and ocular comorbidities were associated with receiving ISBCS. ISBCS represents a potential opportunity to improve access to cataract surgery.

Keratoplasty in the United States: Trends and Indications From 2015 to 2020.

PURPOSE: The aim of this study was to report trends in keratoplasty techniques and indications in the United States from 2015 to 2020. METHODS: This retrospective review of annual reports from the Eye Bank Association of America assessed domestic corneal graft distribution and surgical indication data for various types of keratoplasty. Trends in procedure volume and indications from 2015 to 2020 were analyzed using the Cochran-Armitage test. RESULTS: The total number of corneal transplants increased from 47,903 in 2015 to 49,143 in 2019, with a decline to 42,257 in 2020, most likely due to COVID-19. Penetrating keratoplasty (PK) volume decreased from 2015 to 2020 (19,160-15,402, 40% to 36.4%, P < 0.001), continuing a trend from the previous decade. Descemet membrane endothelial keratoplasty as a percentage of all keratoplasty procedures increased (9.8%-27.8%, P < 0.001), whereas Descemet stripping automated endothelial keratoplasty (47%-33.9%, P < 0.001) and anterior lamellar keratoplasty (ALK) decreased (2.3%-1.2%, P < 0.001).From 2017 to 2020, repeat corneal transplant was the most common specific indication for PK while ectasias/thinnings decreased in prevalence (15.6%-11.5%, P < 0.001). Ectasias/thinnings and endothelial dystrophy remained the leading indications for ALK and endothelial keratoplasty, respectively. CONCLUSIONS: From 2015 to 2020, keratoplasty trends in the United States showed a continuation of the decrease in PK and increase in Descemet membrane endothelial keratoplasty observed in the previous decade. The most common domestic indications from 2017 to 2020 have been repeat corneal graft, endothelial dystrophy, and ectasias/thinnings for PK, EK, and ALK, respectively.

Bilateral EK Rejection After COVID-19 Vaccine.

ABSTRACT: Owing to its rapid development, short-term and long-term effects of the COVID-19 vaccine are still not well understood. This case report highlights bilateral corneal endothelial graft rejection after administration of the Pfizer COVID-19 vaccine. A 73-year-old woman with bilateral Descemet stripping endothelial keratoplasty presented with bilateral decreased visual acuity, ocular pain, and photophobia after her second dose of the Pfizer-BioNTech COVID-19 vaccine. Two weeks after vaccine administration, the uncorrected visual acuity was 20/70 and 20/40. Central corneal thickness as measured by ultrasound was 809 and 825 µm and by Scheimfplug imaging was 788 and 751 µm at the pupil center. Slit-lamp biomicroscopy revealed quiet conjunctiva and sclera but was significant for thickened corneas with Descemet folds in both eyes. The patient was instructed to use prednisolone acetate 1% every 1 to 2 hours with Muro ointment at bedtime.

Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation.

PURPOSE: Since the exact development of posterior subcapsular cataracts (PSCs) is poorly understood, we review various risk factors and propose a two-stage etiology for PSCs. METHODS: The biological mechanisms associated with age-related cataracts (primarily nuclear cataracts, cortical cataracts and PSCs) were reviewed in relation to selected risk factors that induce PSCs (including atopy, diabetes, hypoparathyroidism, myopia, retinitis, solar radiation, steroid use, uveitis, vitrectomy and ionizing radiation). We particularly focused on ionizing radiation, as this is known to be a risk factor specific to PSCs. Based on an analysis of the reviewed material, we propose a detailed explanation of the etiology of PSCs. CONCLUSIONS: Lens epithelial cells (LECs) and lens fiber cells are normally hypoxic and therefore very sensitive to changes in oxidative stress, as quantified by the radiation oxygen effect. We hypothesize that the development of PSC opacities is a two-stage process. Stage I, early in life, is driven by risk factors that promote oxidative stress and ion-pump disruption, harming lens fibers and causing aberrant LECs to proliferate and ectopically migrate as Wedl cells (perhaps by processes associated with an epithelial to mesenchymal transition) to the posterior pole region. After a latent period, in Stage II, the development of PSCs advances mainly due to chronic inflammation and other premature aging-related mechanisms that promote mature vacuolar or plaque PSC. This two-stage hypothesis of PSC etiology accounts for risk factors, such as aging, diabetes and ionizing radiation, which directly affects LECs and the lens. In addition, these risk factors can damage other ocular regions, such as the retina and vitreous, that also indirectly contribute to the development of PSCs. It is possible that the incidence of PSCs may be reduced by reversing the effects of Stage I through various means, including ocular antioxidants.