The association of stroke with herpes zoster ophthalmicus.

BACKGROUND/OBJECTIVES: Studies have reported an association between herpes zoster ophthalmicus (HZO) and stroke. We sought to validate this association with rigorous controls for both medical comorbidities and social factors using a nationwide U.S. administrative medical claims database. SUBJECTS/METHODS: A two-step approach was taken: first a retrospective case-control study was performed, followed by a self-controlled case series (SCCS). For the case control study, cox proportional hazard regression with inverse proportional treatment weighting assessed the hazard for stroke. In the SCCS, incidence of stroke was compared prior to and after the diagnosis of HZO. RESULTS: For the case-control study, 25,720 cases and 75,924 controls met our eligibility criteria. 1712 (6.7%) and 4544 (6.0%) strokes occurred in the case and control groups respectively, conferring an 18% increased risk of stroke in the observed 1-year post-HZO period (HR = 1.18, 95% CI: 1.12-1.25, p < 0.001). SCCS analysis showed the risk for stroke was highest in the month immediately after HZO episode compared to any other time range (1-30 days after, relative risk 1.58, p < 0.001) and even higher when assessing time more distal time points prior to the HZO diagnosis (days 1-30 after HZO diagnosis had RR = 1.69 (95% CI: 1.38-2.07) and RR = 1.93 (95% CI: 1.55-2.39) compared with days -120 to -91 and -150 to -121 prior to index, respectively (p < 0.001). CONCLUSIONS: After accounting for stroke risk factors, our analysis confirms the association between HZO and stroke, with highest risk in the immediate month after an episode.

Real-world socioeconomic determinants of corneal crosslinking in a national cohort.

PURPOSE: To characterize recent socioeconomic trends in patients with keratoconus/corneal ectasias undergoing corneal crosslinking (CXL). SETTING: A deidentified administrative medical claims database comprised commercial and Medicare Advantage health claims from across the United States. DESIGN: Population-based retrospective cohort study. METHODS: This study identified 552 patients with keratoconus/corneal ectasia who underwent CXL and 2723 matched controls who did not undergo CXL based on Current Procedural Terminology coding from a U.S. national insurance claims database from 2016 to 2020. For each patient, characteristics, including sex, race, age, household net worth, education level, insurance plan type, and geographic region, were extracted. Multivariate logistic regression was conducted to determine the odds of undergoing crosslinking. RESULTS: Age 30 years or older (odds ratio [OR], 0.34, P < .001) was associated with decreased likelihood of undergoing CXL. Sex, race, education, and patient income were not associated with odds of undergoing CXL. Patients with health maintenance organization insurance had lower odds of undergoing CXL (OR, 0.64, P = .047). Geographically, patients on the east coast (OR, 0.37, P < .001) and Lower Midwest (OR, 0.31, P < .001) had statistically lower odds of undergoing crosslinking. CONCLUSIONS: This is the first study to identify socioeconomic determinants of CXL, and it highlights that geographic location and insurance type may limit accessibility to patients.

Anatomic and visual outcomes of corneal transplantation during infancy.

PURPOSE: To determine the effect of age at penetrating keratoplasty (PKP) on graft survival and visual outcome in children with corneal opacities transplanted during infancy. METHODS: In this two-center retrospective consecutive cohort study, the medical records of infants who underwent unilateral or bilateral PKP during the first year of life between 2004 and 2011 were reviewed retrospectively. PKP was categorized as early (age 0-90 days) or late (age 91-365 days). Main outcome measures were graft survival and vision (classified as poor, fair, or good, considering both testing method and age norms). RESULTS: A total of 62 eyes of 52 infants were included: 19 eyes underwent early PKP; 43 eyes, late PKP. Of the 62 eyes, 61 had central congenital corneal opacities; 1 was acquired. Median follow-up was 38.1 months (range, 12.2-150.5 months). Kaplan-Meier graft survival estimates were 0.92 at 1 year (95% CI, 0.81-0.96) and 0.61 at 5 years (0.44-0.74). Graft survival (early PKP, 73.7%; late PKP, 65.1% [P = 0.57]) did not differ between groups. Of the 55 eyes with recorded visual acuities, no significant difference existed in proportion with ambulatory or better vision at latest follow-up between early and late PKP (42.1% vs 55.6%; P = 0.61). CONCLUSIONS: Visual outcomes were better for PKP performed during infancy compared to results of prior reports of late PKP; however, clearing of congenital opacities in the first 3 months of life did not improve visual outcomes compared to later PKP. One-half of grafts survived >5 years. Early PKP did not worsen graft survival, but PKP may be technically easier to perform later in infancy.

Cytomegalovirus retinitis in an immunocompetent host after complicated cataract surgery.

PURPOSE: To report a case of an immunocompetent patient who developed cytomegalovirus (CMV) retinitis after complicated cataract surgery resulting in aphakia. OBSERVATIONS: A 67-year-old man with type 2 diabetes developed retinitis six months after cataract surgery that resulted in aphakia. Anterior chamber DNA testing was positive for CMV. Comprehensive systemic work-up revealed no immune insufficiency. The retinitis was successfully treated with intravitreal foscarnet and extended oral valgancyclovir treatment, however, he subsequently developed rhegmatogenous retinal detachment. CONCLUSION AND IMPORTANCE: CMV retinitis may occur in immunocompetent patients in the setting of aphakia and prolonged topical steroid use.

The use of self-retained, cryopreserved amniotic membrane for the treatment of Sjögren syndrome: a case series.

PURPOSE: To determine whether signs and symptoms of ocular surface disease improve after placement of a self-retained, cryopreserved amniotic membrane (CAM) in patients with Sjögren syndrome (SS). METHODS: The medical records of SS patients who received a self-retained CAM implant (Prokera or Prokera Slim; TissueTech Inc, Doral, FL) for the treatment of ocular surface disease between August 2012 and August 2016 at a single, large academic institution were reviewed retrospectively. Visual acuity, results of slit-lamp examination of the cornea and conjunctiva, and dry eye symptoms, were evaluated before and after CAM insertion. RESULTS: A total of 6 eyes of 6 patients (all female; mean age, 62.5 ± 13.0 years [range, 49-86 years]) were included. All patients were on topical medications at the time of the study and had signs of ocular surface dryness. There were reductions in corneal and/or conjunctival staining in 5 eyes (83%) after the CAM dissolved. All patients who completed therapy (5/5) experienced a relapse in their signs and symptoms within 1 month of removal of the CAM, with an average time to relapse of 24.6 days. Mean follow-up time was 54.5 days. Foreign body sensation and blurred vision were the most common complaints associated with the CAM implant. CONCLUSIONS: In this small case series, self-retained CAM implantation was found to be beneficial in SS patients with ocular surface disease that is refractory to standard therapies; however, we found that the effects were temporary. Future larger studies are needed to confirm these benefits.

Survey of Ophthalmologists Regarding Practice Patterns for Dry Eye and Sjogren Syndrome.

OBJECTIVE: To survey ophthalmologists about current practice patterns regarding the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS) workup. METHODS: An online survey was sent to ophthalmologists affiliated with the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015. Descriptive statistics were used to summarize the data. RESULTS: Four hundred seventy-four survey invitations were sent out and 101 (21%) ophthalmologists completed the survey. The common traditional dry eye test performed was corneal fluorescein staining (62%) and the most common newer dry eye test performed was tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry eye patients for SS workups, with 18% reporting that they never refer any patients. The most common reasons for referrals included positive review of systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye that is refractory to treatment (42%). The majority (83%) felt that there is a need for an evidence-based standardized screening tool for dry eye patients to decide who should be referred for evaluation for SS. CONCLUSIONS: Ophthalmologists continue to prefer the use of traditional dry eye tests in practice, with the most common test being corneal fluorescein staining. There is an underreferral of dry eye patients for SS workups, which is contributing to the continued underdiagnosis of the disease. Most respondents felt that there was a need for an evidence-based standardized screening tool to decide which dry eye patients should be referred for SS evaluations.

Trends in Corneal Transplantation in Keratoconus.

PURPOSE: To determine recent trends in and sociodemographic/comorbid conditions associated with penetrating keratoplasty (PK) and lamellar keratoplasty (LK) for keratoconus (KCN). METHODS: Patients with KCN and subsequent PK and LK procedures were identified using International Classification of Diseases, 9th revision (ICD-9) and Current Procedural Terminology (CPT) billing codes. The change in surgical rates was calculated over a decade, and multivariate analysis demonstrated factors associated with undergoing surgery. RESULTS: A total of 21,588 patients with KCN underwent 1306 PK procedures and 109 LK procedures during the study period. Individuals were significantly less likely to undergo PK from 2009 to 2012 compared with 2001 to 2008 [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.47-0.68, P < 0.001]. Multivariate analysis revealed the factors that increased the likelihood of PK alone and included age 20 to 40 (OR 1.90, 95% CI, 1.19-3.04, P < 0.001), black race (OR 1.36, 95% CI, 1.06-1.74, P = 0.01), and education less than a bachelor's degree or only a high school diploma (OR 1.94-2.84, P < 0.001 for all comparisons). Female sex (OR 0.74, 95% CI, 0.63-0.88, P < 0.001) and household net worth either between 150 and 249k (OR 0.64, 95% CI, 0.48-0.84, P < 0.001) or more than $500,000 (OR 0.71, 95% CI, 0.51-0.99, P = 0.03) were traits associated with decreased odds of PK. No significant associations for LK were observed. CONCLUSIONS: The rate of PK in KCN is decreasing in the United States. The third or fourth decade of life, male sex, black race, lower education, and greater household net worth are associated with increased odds of PK.

Bilateral Urrets-Zavalia Syndrome After Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To report a case of bilateral Urrets-Zavalia syndrome (UZS) after Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Case report. RESULTS: A 61-year-old patient with Fuchs endothelial dystrophy initially developed UZS in the left eye after DSAEK. Thirteen months later, she underwent combined cataract surgery and DSAEK in the right eye, and postoperatively she was noted to have elevated intraocular pressure and a fixed and dilated pupil on the first postoperative day. Both pupils showed partial improvement in reactivity over the course of weeks to months. This is the first case of bilateral UZS after DSAEK surgery and in a patient with Fuchs dystrophy. CONCLUSIONS: UZS may occur bilaterally after DSAEK. Because elevated intraocular pressure has been shown to be a risk factor for this condition, this should be monitored closely during the postoperative period.

Acute onset anterior uveitis after darbepoetin alfa infusion.

A 79-year-old female with a 2-month history of newly diagnosed myelodysplastic syndrome for which she received blood transfusion with darbepoetin alfa presented with bilateral anterior uveitis 1 day after her fourth transfusion. On exam, visual acuity was 20/20 in both eyes with biomicroscopy notable for conjunctival injection and anterior chamber cell and flare consistent with anterior uveitis. She had no systemic symptoms, no history of eye trauma, and no known infections. This case, along with prior reports in the literature, suggests that anterior uveitis may be an idiosyncratic complication of darbepoetin alfa therapy.

Treatment of ocular surface squamous neoplasia with topical Aloe vera drops.

PURPOSE: To report a case of ocular surface squamous neoplasia (OSSN) that resolved with topical Aloe vera eye drop treatment. METHODS: A 64-year-old Hispanic woman with a lesion typical for OSSN in her left eye was followed up with multiple clinical examinations and ocular surface photographs to document changes over time with A. vera-based topical treatment. RESULTS: The patient refused biopsy of her lesion and traditional treatments and, instead, initiated using A. vera eye drops 3 times daily. At follow-up visits, the lesion was noted to regress until it finally resolved 3 months after commencing treatment. No additional topical medications were used, and she has remained tumor free for 6 years. CONCLUSIONS: Ongoing research is warranted because A. vera may represent a new therapeutic class of medications for OSSN treatment.

A significant drug-drug interaction detected through corneal examination: resolution of cornea verticillata while using amiodarone.

PURPOSE: To describe a patient with resolution of cornea verticillata while still using amiodarone as a result of a drug interaction lowering serum levels of amiodarone. METHODS: An 83-year-old retired physician with long-standing cornea verticillata was noted to have complete resolution of cornea verticillata on a routine follow-up eye examination. The patient reported complete compliance with using amiodarone daily, with no recent changes in dosage or formulation. Despite this, he reported a recent increase in the frequency of palpitations. He had recently started rifampin for treatment of tuberculosis. RESULTS: Serum amiodarone and desethylamiodarone levels were obtained and found to be below therapeutic range. After rifampin was discontinued, serum amiodarone and desethylamiodarone levels increased to a therapeutic range and cornea verticillata returned after 4 months. CONCLUSIONS: In patients currently using amiodarone, clearing of cornea verticillata should alert the ophthalmologists to the possibility of decreased serum amiodarone levels.

Posterior polymorphous dystrophy associated with nonkeratoconic steep corneal curvatures.

PURPOSE: To report a case series of eyes with posterior polymorphous corneal dystrophy and steep nonkeratoconic corneas. METHODS: Retrospective, descriptive, nonrandomized case series. RESULTS: Thirty-five eyes of 18 patients (14 cases from 6 families and 4 isolated cases) with diffuse posterior polymorphous corneal dystrophy had mean topographic simulated keratometry readings of 52.21 diopters (D), with a range of 46.47 D to 59.86 D and an SD of 3.69 D, with no slit-lamp or topographic findings suggestive of keratoconus. CONCLUSIONS: The patients in this series demonstrate diffuse posterior polymorphous corneal dystrophy and nonkeratoconic steep corneas.

Corneal edema and haze after selective laser trabeculoplasty.

PURPOSE: To report 2 cases of corneal edema, haze, and thinning in patients after undergoing selective laser trabeculopasty. METHODS: Selective laser trabeculoplasty was performed for the treatment of primary open-angle glaucoma on 2 patients who subsequently developed corneal stromal haze within 24 to 48 hours of the procedure. RESULTS: The patients were treated with topical steroids for several weeks. Although their corneal edema resolved, both patients were left with residual corneal scarring and thinning. One patient had a significant hyperopic shift. CONCLUSIONS: Corneal edema, haze, and thinning after selective laser trabeculoplasty is an extremely rare event, with only 2 other cases reported in the literature. Although certain causes are postulated to play a role in this complication, it is not yet understood what may predispose a patient to corneal changes as a result of this laser procedure.

Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness.

Leber's congenital amaurosis (LCA) is a group of severe inherited retinal degenerations that are symptomatic in infancy and lead to total blindness in adulthood. Recent clinical trials using recombinant adeno-associated virus serotype 2 (rAAV2) successfully reversed blindness in patients with LCA caused by RPE65 mutations after one subretinal injection. However, it was unclear whether treatment of the second eye in the same manner would be safe and efficacious, given the potential for a complicating immune response after the first injection. Here, we evaluated the immunological and functional consequences of readministration of rAAV2-hRPE65v2 to the contralateral eye using large animal models. Neither RPE65-mutant (affected; RPE65(-/-)) nor unaffected animals developed antibodies against the transgene product, but all developed neutralizing antibodies against the AAV2 capsid in sera and intraocular fluid after subretinal injection. Cell-mediated immune responses were benign, with only 1 of 10 animals in the study developing a persistent T cell immune response to AAV2, a response that was mediated by CD4(+) T cells. Sequential bilateral injection caused minimal inflammation and improved visual function in affected animals. Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials.

Presumed corneal copper deposition and oral contraceptive use.

PURPOSE: To report a case of presumed bilateral corneal copper deposition secondary to oral contraceptive use. METHODS: A 23-year-old woman was referred for evaluation of bilateral corneal opacities. The location of the deposits deep in Descemet's membrane and appearance made copper deposition a likely consideration. RESULTS: Subsequent laboratory results revealed an elevated serum copper level (189 µg/dL). Other causes of cupremia were subsequently ruled out, and the patient's corneal copper deposition was attributed to her oral contraceptive use. With cessation of the oral contraceptive, her serum copper levels normalized, but the corneal deposits remained after 5 months of follow up. CONCLUSION: To our knowledge, we report the first case in the ophthalmic literature of presumed corneal copper deposition in the setting of oral contraceptive use. It is important to recognize the corneal findings associated with copper deposition, because it may lead to the diagnosis and treatment of other serious systemic conditions causing elevated serum copper levels.

Development of epithelial downgrowth several decades after intraocular surgery.

PURPOSE: To report the management of a patient with the longest reported interval between intraocular surgery and the development of epithelial downgrowth. METHODS: A 53-year-old man who underwent right eye penetrating keratoplasty in 1970 for keratoconus and removal of an iris cyst in 1977 developed epithelial downgrowth 25 years after cyst removal. RESULTS: The area of epithelial downgrowth was initially treated with cryotherapy. Two weeks postoperatively, the patient had no resolution of epithelial downgrowth and developed diffuse corneal edema. Penetrating keratoplasty was performed along with extracapsular cataract extraction. At 6 months of follow-up, the patient's graft was clear, without evidence of recurrence of epithelial downgrowth, and he had 20/50 visual acuity. CONCLUSION: Epithelial downgrowth is an uncommon yet serious complication of intraocular surgery, making early detection of this condition important. This case illustrates that epithelial downgrowth can occur several decades after intraocular surgery.

Intraocular caterpillar setae without subsequent vitritis or iridocyclitis.

PURPOSE: To report a case of caterpillar setae embedded in the corneal stroma and inferotemporal retina with minimal inflammation. DESIGN: Observational case report. METHODS: A 4-year-old boy developed a red eye after playing with a caterpillar. He was placed on topical tobramycin/dexamethasone and referred for evaluation of embedded setae in his conjunctiva, cornea, iris, and retina. Examination revealed no iridocyclitis or vitritis. RESULTS: Because of the lack of intraocular inflammatory response, no invasive intervention was conducted to remove or destroy the setae and he was tapered off the tobramycin/dexamethasone. At 4-month follow-up he remained asymptomatic with the setae still present in both his cornea and retina. In addition, vitreous membranes had formed in the immediate vicinity of the intraretinal setae. CONCLUSION: Intraretinal and corneal setae can be embedded with minimal inflammation and can be tolerated without need for surgical intervention.