Pediatric Phlyctenular Keratoconjunctivitis at a Tertiary Care Center in the United States.

PURPOSE: The aim of this study was to evaluate characteristics and outcomes of pediatric phlyctenulosis at a tertiary care center in the United States. METHODS: A retrospective cohort study of phlyctenulosis diagnosis in patients younger than 18 years was conducted. Demographics, presenting features, treatment regimens, and outcomes were analyzed. RESULTS: Seventy patients (95 eyes) with phlyctenulosis were identified. Fifty-four patients (77.1%) were Hispanic, which was greater than the center's proportion of pediatric patients identifying as Hispanic (53.8%, P < 0.0001). Common comorbidities included adjacent external/lid disease (82.9%), allergic/atopic disease (18.6%), and viral infections (8.6%). Nine patients had tuberculosis testing which was negative in all cases. Five patients had vitamin A testing which revealed deficiency in 1 patient. Treatment regimens were diverse and included varying combinations of topical and systemic medications. Complications included corneal scarring (27.4%), corneal neovascularization (40.0%), amblyopia (16.8%), corneal perforation (3.2%), and severe limbal stem-cell deficiency (1.1%). 26.3% of affected eyes had final visual acuity worse than 20/40. Differences in rates of corneal complications between Hispanic and non-Hispanic patients were not statistically significant, although severe corneal complications including perforation occurred only in the Hispanic group. CONCLUSIONS: This study presents a modern cohort of phlyctenulosis at a tertiary center in the United States and includes a larger proportion of Hispanic patients than expected. Phlyctenulosis carries high corneal morbidity and may frequently result in reduced visual acuity. Similar rates of corneal complications were seen in Hispanic versus non-Hispanic patients, but severe corneal complications were seen only in the Hispanic group.

Bilateral posterior central corneal steepening with decreased visual acuity.

A 40-year-old woman was referred for the assessment of bilateral corneal opacities with gradual visual decline over the course of the past decade. Her past ocular history is significant for bilateral amblyopia and strabismus surgery in both eyes before age 5. The patient's parents were told by her childhood ophthalmologist that she had a hereditary disorder. Her systemic review was significant for anal fissure and human leukocyte antigen-B27 ankylosing spondylitis. Her past ocular record revealed corrected distance visual acuity (CDVA) of 20/80 in both eyes in 2018 with central corneal haze. On presentation, her uncorrected distance visual acuity was 20/150 in both eyes. Her CDVA was 20/100 in both eyes with manifest refraction of +0.50 -2.50 × 075 in the right eye and +5.00 -2.25 × 094 in the left eye. Corneal topography reflected keratometry of 35.75/38.97 × 171 in the right eye and 36.45/38.35 × 32 in the left eye. Central corneal thickness was 669 µm and 652 µm, respectively. External slitlamp examination revealed a central faint stromal opacity inferior to the visual axis in the right eye and a central faint stromal opacity in the left eye, and both were associated with steep posterior curvature of the cornea (Figure 1). Further findings included 0.5 corneal haze with mild guttata, normal irides, and clear lenses in both eyes. Intraocular pressure was 23 mm Hg and 26 mm Hg, respectively (Figure 2, Supplemental Figures 1 and 2, http://links.lww.com/JRS/A543). Gonioscopy was unremarkable. Dilated fundus examination revealed a 0.15 cup-to-disc ratio bilaterally, but otherwise no pertinent vitreoretinal pathologies were noted. What is the most likely diagnosis? What medical or surgical interventions would you recommend for this patient? What is the prognosis for this patient?

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Management of Congenital Aniridia-Associated Keratopathy: Long-Term Outcomes from a Tertiary Referral Center.

PURPOSE: To report the outcomes of medical and surgical management for congenital aniridia-associated keratopathy (AAK) over a long-term follow-up period. DESIGN: Retrospective, comparative case series. METHODS: Medical records of patients diagnosed with congenital aniridia were retrospectively reviewed. Age, sex, ethnicity, follow-up time, AAK stage, noncorneal abnormalities, ocular surgeries, and complications were recorded. The visual acuity equivalent (VAE), approximate Early Treatment Diabetic Retinopathy Study (appETDRS) letter score, was calculated using recorded Snellen visual acuities. RESULTS: A total of 92 eyes of 47 patients (31 females) with mean age of 48.0 ± 18.0 years and mean follow-up of 78.6 ± 42.2 months were included. At the initial visit, 12 eyes (13%) were classified as Stage I AAK, 33 eyes (35.9%) were Stage II, 25 eyes (27.2%) were Stage III, 17 eyes (18.5%) were Stage IV, and 5 eyes (5.4%) were Stage V. Limbal stem cell transplantation (LSCT) and Boston keratoprosthesis (KPro) were frequently performed in eyes with Stages III-V. These advanced corneal surgeries significantly improved the median (95% confidence interval [CI]) of calculated appETDRS scores from 2 (0-20) to 26 (15-41) (Snellen values, 20/20,000 to 20/300; P = 0.0004). Patients with earlier Stages (I-II) of AAK were managed medically and had stable visual acuity through their final visits (appETDRS score of 26 [20-35] to 35 [26-35]; Snellen, 20/300 to 20/200; P > 0.05). The appETDRS VAE was significantly improved from 20 (0-35) to 30 (20-55), Snellen, 20/400 to 20/250, following LSCT (P = 0.021) and from 2 (0-20) to 2 (0-41) after KPro; Snellen, 20/20,000 VAE but with improved 95% CI after follow-up (P = 0.019). CONCLUSIONS: With proper characterization and staging of AAK, individualized medical and advanced surgical interventions preserves and improves visual acuity.

Recognition of Fungal Keratitis in Boston Type I Keratoprosthesis: Importance of Awareness and Novel Identification of Exophiala phaeomuriformis.

PURPOSE: To present a case of Exophiala phaeomuriformis fungal keratitis to demonstrate the heightened concern for fungal infection in patients with a keratoprosthesis and to highlight the rare involvement of Exophiala phaeomuriformis. METHODS: Case report. RESULTS: Exophiala phaeomuriformis was identified in a susceptible patient 7 years after Boston type I keratoprosthesis (KPro) implantation. CONCLUSIONS: Although fungal infiltration after KPro placement does not represent a novel clinical infection, identification of the rare Exophiala species in a patient with a KPro has not been reported and provides an opportunity for reflection on fungal identification, prophylaxis, and prevention in this vulnerable patient population.

Keratoconus and Other Corneal Diseases: Pharmacologic Cross-Linking and Future Therapy.

The ability to cross-link collagen fibers and use this technique to strengthen the cornea has become of great interest to ophthalmologists in the last decade. For progressive diseases such as keratoconus, collagen cross-linking confers the possibility of halting progression and stabilizing the cornea, a benefit that is not observed with any other current treatment. Collagen cross-linking uses riboflavin combined with ultraviolet A light to induce the formation of bonds between collagen fibrils that strengthen the cornea. This chapter will discuss the theory, technique, indications, and complications of corneal cross-linking. Much of what will be discussed is in areas of active research that will likely be further clarified as more experience is gained with this procedure.

Epithelial Ingrowth Following Endothelial Keratoplasty.

PURPOSE: To present a large case series of epithelial ingrowth or implantation following endothelial keratoplasty (EK) with the purpose of identifying the common causes as well as the various clinical presentations. We aim to determine the typical clinical course and the most effective treatment for this rare but serious complication. METHODS: This is a retrospective study of 13 patients who developed epithelial ingrowth or implantation post-EK. Slit lamp photographs were independently examined along with other diagnostic imaging and histopathology to confirm the diagnosis. Patient medical records including operative reports were reviewed to determine the number of surgeries that occurred before EK and details of surgical technique, for example, whether venting incisions were performed. Records from follow-up visits were reviewed to determine the natural progression and management of these cases. The literature was reviewed and a meta-analysis was performed. RESULTS: The patients were divided into 5 groups according to the type of epithelial presentation. Eight patients had involvement within the interface away from the visual axis. One patient had ingrowth in the interface within the visual axis, 2 had retrocorneal involvement, and 1 had anterior chamber involvement. One had both retrocorneal and anterior chamber involvement. Venting incisions were performed in 8 patients, but only 1 had ingrowth related to the venting incision. Nine patients were observed without evidence of significant progression. Four patients had surgical treatment to remove the epithelium. CONCLUSIONS: Epithelial ingrowth or implantation occurs most commonly within the interface away from the visual axis and typically does not progress. The presentation of a homogeneous gray-white interface opacity is characteristic. Ingrowth can result from venting incisions, but rarely does. Other causes are eccentric trephination or loose donor or host epithelium being dragged into the eye at the time of surgery.

Clostridium perfringens endophthalmitis after penetrating keratoplasty with contaminated corneal allografts: a case series.

PURPOSE: To report the postoperative clinical course of 3 patients who underwent corneal transplantation with corneal allografts contaminated with Clostridium perfringens and to evaluate the risk factors for anaerobic contamination in 2 donors. METHODS: Patient records and adverse reaction reports from a single eye bank related to cases of posttransplant C. perfringens endophthalmitis were reviewed. Records regarding the mated corneas, donor autopsy reports, and other pertinent data were also reviewed. RESULTS: Three adverse reactions associated with transplantation of corneal allografts contaminated with C. perfringens were reported. Two cases were from mated corneas. Both patients developed fulminant endophthalmitis after undergoing uncomplicated penetrating keratoplasty and required subsequent enucleation. Another isolated case (with no adverse reaction in the mate cornea) developed hypopyon postoperatively that resolved with intravitreal and topical antibiotics. Possible risk factors for anaerobic tissue contamination in the donors included illicit drug use in the first donor and exposure to sewage at the time of death in the second donor. CONCLUSIONS: Clostridial endophthalmitis is an aggressive rapidly progressive infection with potentially poor visual outcomes that can be transmitted from infected corneal allografts. Further investigation is needed to clarify the role of anaerobic donor rim cultures and the donor risk factors associated with recovering corneal allograft tissue contaminated with C. perfringens.

The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study.

OBJECTIVE: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age. DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years. METHODS: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. MAIN OUTCOME MEASURES: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months. RESULTS: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P<0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6. CONCLUSIONS: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease.

Increased expression of secreted frizzled-related protein-1 and microtubule-associated protein light chain 3 in keratoconus.

PURPOSE: To study the expression of secreted frizzled-related protein-1 (SFRP-1) and microtubule-associated protein light chain 3 (LC3), an autophagy marker, in keratoconus. METHODS: Under an institutional review board-approved protocol, de-identified and/or surgically discarded normal donor (n = 10) and keratoconus corneas (n = 10) were obtained. The corneal samples were fixed in formalin and embedded in paraffin. Immunohistochemical staining using SFRP-1 and LC3 antibodies was performed. RESULTS: The majority of expression of SFRP-1 was seen in the epithelium; however, in 3 tissues that showed high expression, staining was also present in the stroma and endothelium. Like SFRP-1, the LC3 expression in keratoconus tissues occurred at 3 different levels: low, medium, and high. Collectively these data suggest that there are differences in the expression levels of SFRP-1 and LC3 in keratoconus tissue compared with the normal tissue. Low expressivity of SFRP-1 seemed to correspond to low expressivity of LC3, whereas medium to high expressivity of SFRP-1 corresponded to medium to high expressivity of LC3. CONCLUSIONS: Increased expression of SFRP-1 and LC3 was observed in keratoconus corneas. Keratocyte autophagy seen with keratoconus may play a role in the pathogenesis of keratoconus.

Relationship Between Fuchs Endothelial Corneal Dystrophy Severity and Glaucoma and/or Ocular Hypertension.

OBJECTIVE To investigate whether Fuchs endothelial corneal dystrophy (FECD) severity is associated with glaucoma and/or ocular hypertension (G/OHTN). METHODS A subset of eyes (n = 1610) from the FECD Genetics Multi-Center Study were examined to estimate the association between FECD severity (grades 0-6 based on guttae confluence) and G/OHTN. Logistic regression models that accounted for the correlation between eyes and adjusted for age, sex, central corneal thickness, intraocular pressure, presence of diabetes, and time of day of the initial evaluation were fit. RESULTS A total of 107 eyes (6.6%) had G/OHTN based on the study definition. The prevalence of G/OHTN in the control group was 6.0%. The prevalence was lower in index cases with an FECD grade of 1 through 3 and family members with a grade of 0 or 1 through 3 (0.0% and 2.1%, respectively) but higher in index cases and family members with a grade of 4 through 6 (11.2% and 8.5%, respectively). Adjusting for covariates, eyes with a grade of 4 through 6 were more likely to have concurrent G/OHTN than eyes with no FECD (index cases vs controls: odds ratio [OR] = 2.10, P = .04; affected vs unaffected family members: OR = 7.06, P = .07). Age (OR = 1.06 per 1-year increase, P < .001) and intraocular pressure (OR = 1.15 per 1-mm Hg increase, P < .001) were also associated with an increased prevalence of G/OHTN. Sex, diabetes, time of day of evaluation, and central corneal thickness were not associated with the prevalence of G/OHTN (P ≥ .15). CONCLUSIONS Glaucoma and/or ocular hypertension occurs more often in eyes with severe FECD compared with unaffected eyes. Therefore, it may be beneficial to monitor for the development of glaucoma in these patients.

What causes keratoconus?

PURPOSE: The etiology of keratoconus has been the subject of numerous studies. Here, we review the body of literature that attempts to determine what causes keratoconus. METHODS: A review of the published literature was performed to evaluate the possible causes of keratoconus and how the different etiologies may play a role in the development of this disease. RESULTS: Peer-reviewed published papers and recent abstracts concerning the different etiologies of keratoconus were reviewed and discussed. Biochemical, genetic, and environmental factors are reviewed. The role of eye rubbing and atopic disease are explored. CONCLUSIONS: We agree with the hypothesis that there is a genetic predisposition that requires a "second hit" or environmental event to elicit progressive disease in keratoconus. Eye rubbing may serve as the "second hit" in some predisposed individuals. Inflammatory mediator studies question if keratoconus is really a noninflammatory thinning disorder of the cornea.

Boston type I keratoprosthesis for visual rehabilitation in a patient with gelatinous drop-like corneal dystrophy.

PURPOSE: To report the use of a Boston type I keratoprosthesis as a primary penetrating procedure to treat gelatinous drop-like corneal dystrophy (GDLD), with presentation of pathologic findings and discussion of other surgical options. CASE REPORT: A 49-year-old woman with GDLD in both eyes and history of recurrent corneal opacification following multiple superficial keratectomies is presented. Best corrected visual acuity (BCVA) was counting fingers in both eyes. A Boston type I keratoprosthesis was implanted in her left eye after optical iridectomy, extracapsular cataract extraction, and anterior vitrectomy. RESULTS: The surgery was uneventful and one month after surgery, best corrected vision improved to 20/20 and has been maintained for a period of more than 14 months. No post-operative complications were observed. Histopathology of the corneal specimen is presented. CONCLUSIONS: GDLD is a rare disorder of amyloid deposition. Recurrence of this condition following surgery is extremely common. Boston type I keratoprosthesis is an effective procedure for restoring vision in affected patients.