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?

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.

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.

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.

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.

Copper deposition in a variant of multiple myeloma: pathologic changes in the cornea and the lens capsule.

PURPOSE: To report the pathologic changes in the cornea and the lens capsule resulting from copper deposition in a variant of multiple myeloma. METHODS: Case report. RESULTS: Light microscopy of the cornea revealed endothelial cell attenuation with diffuse copper deposition in the central Descemet membrane, which showed thinning, whereas copper banding was seen in the midperipheral and peripheral cornea where the Descemet membrane was normal in thickness. Copper deposition was confirmed by x-ray microanalysis. The anterior lens capsule showed subepithelial copper deposits. Thickening, multilayering, and splitting of the lens capsule were also noted. CONCLUSIONS: We report the pattern of deposition of copper in the Descemet membrane of the cornea and the anterior lens capsule in multiple myeloma, associated with hypercupremia. Descemet membrane thinning and regional differences in copper deposition were noted. Also, thickening and splitting of the lens capsule are a novel observation.

Outcome of descemet stripping automated endothelial keratoplasty in patients with an anterior chamber intraocular lens.

PURPOSE: To evaluate the outcome of Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with a retained anterior chamber intraocular lens (ACIOL). METHODS: A retrospective review of 11 patients with corneal decompensation and ACIOL who underwent DSAEK was performed. All patients except 1 had open-loop style ACIOLs, and in all cases, there was adequate anterior chamber depth. At the time of surgery, 6 patients had a temporary suture to secure their graft, 2 of which were retained from the insertion method, and the other 4 were placed additionally. Postoperatively, the rate of donor detachment, graft clarity, corneal pachymetry, and visual acuity were noted. RESULTS: There was only 1 graft dislocation postoperatively, which was reattached successfully by air injection. There was 1 primary graft failure (without dislocation) among the 11 patients during the mean follow-up of 12 months (range: 6-25 months); at last follow-up, the visual acuity had improved in all the other 10 patients. CONCLUSIONS: This series demonstrates that DSAEK can be performed successfully in patients with existing ACIOLs. These early outcomes suggest that DSAEK alone may be considered as an alternative to a lens exchange with DSAEK in patients with adequate anterior chamber depth.

Donor risk factors for graft failure in the cornea donor study.

PURPOSE: The purpose of this study was to assess the relationship between donor factors and 5-year corneal graft survival in the Cornea Donor Study. METHODS: Donor corneas met criteria established by the Eye Bank Association of America, had an endothelial cell density of 2300 to 3300/mm, and were determined to be of good to excellent quality by the eye banks. Donor corneas were assigned using a random approach and surgeons were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines and subjects were followed for 5 years. Donor and donor cornea factors were evaluated for their association with graft failure, which was defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. RESULTS: Graft failure was not significantly associated with the type of tissue retrieval (enucleation versus in situ), processing factors, timing of use of the cornea, or characteristics of the donor or the donor cornea. Adjusting for donor age did not affect the results. CONCLUSION: Donor and donor cornea characteristics do not impact graft survival rates for corneas comparable in quality to those used in this study.

Clinical and histopathologic features of failed descemet stripping automated endothelial keratoplasty grafts.

PURPOSE: To study the histopathologic features of Descemet stripping automated endothelial keratoplasty (DSAEK) grafts removed after graft failure and to correlate with relevant clinical features. METHODS: Retrospective study of 8 cases in 7 patients who experienced DSAEK graft failure during the surgeons' learning phase. Perioperative clinical findings were correlated with pathologic findings of the explanted graft specimens. Imaging software was used to measure the central and peripheral thickness of each graft. RESULTS: Graft failure occurred in association with graft detachment or excessive surgical manipulation. In 4 cases, the donor tissue detached, including 2 cases with routes for bubble escape. In 3 cases, the graft remained attached but failed to clear. The mean preoperative DSAEK button thickness was 205 +/- 61.8 microm. Average death to preservation time was 8 hours 47 minutes, and average preservation to surgery time was 2 days 22 hours. By light microscopy, explanted donor tissue showed varying degrees of keratocyte degeneration and marked endothelial cell loss. Two specimens with bubble escape had less endothelial loss, and 1 specimen showed epithelial ingrowth at the interface. Repeat keratoplasty (5 DSAEK, 2 penetrating keratoplasty) was successful in 6 of 7 cases. CONCLUSIONS: This series correlates factors that may play a role in DSAEK failure with histopathologic features of explanted DSAEK lenticules. Marked endothelial loss was common in cases with surgical trauma but was less in cases with bubble escape. One specimen showed an epithelial membrane on the stromal interface. Outcomes of repeat DSAEK in these patients seem promising.

The effect of donor age on corneal transplantation outcome results of the cornea donor study.

OBJECTIVE: To determine whether graft survival over a 5-year follow-up period using corneal tissue from donors older than 65 is similar to graft survival using corneas from younger donors. DESIGN: Multicenter prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema); 11 subjects with ineligible diagnoses were not included. METHODS: Forty-three participating eye banks provided corneas from donors in the age range of 12 to 75 with endothelial cell densities of 2300 to 3300 cells/mm(2), using a random approach without respect to recipient factors. The 105 participating surgeons at 80 sites were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Subjects were observed for 5 years. MAIN OUTCOME MEASURES: Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of 3 consecutive months. RESULTS: The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the >/=66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups. CONCLUSIONS: Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors >/= 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.

Donor age and corneal endothelial cell loss 5 years after successful corneal transplantation. Specular microscopy ancillary study results.

OBJECTIVE: To determine whether endothelial cell loss 5 years after successful corneal transplantation is related to the age of the donor. DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: Three hundred forty-seven subjects participating in the Cornea Donor Study who had not experienced graft failure 5 years after corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema). TESTING: Specular microscopic images of donor corneas obtained before surgery and postoperatively at 6 months, 12 months, and then annually through 5 years were submitted to a central reading center to measure endothelial cell density (ECD). MAIN OUTCOME MEASURE: Endothelial cell density at 5 years. RESULTS: At 5 years, there was a substantial decrease in ECD from baseline for all donor ages. Subjects who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 69% in the study eye, resulting in a 5-year median ECD of 824 cells/mm(2) (interquartile range, 613-1342), whereas subjects who received a cornea from a donor 66 to 75 years old experienced a cell loss of 75%, resulting in a median 5-year ECD of 654 cells/mm(2) (interquartile range, 538-986) (P [adjusted for baseline ECD] = 0.04). Statistically, there was a weak negative association between ECD and donor age analyzed as a continuous variable (r [adjusted for baseline ECD] = -0.19; 95% confidence interval, -0.29 to -0.08). CONCLUSIONS: Endothelial cell loss is substantial in the 5 years after corneal transplantation. There is a slight association between cell loss and donor age. This finding emphasizes the importance of longer-term follow-up of this cohort to determine if this relationship affects graft survival.

Atypical ocular presentations of Rosai-Dorfman disease.

PURPOSE: To report atypical ocular findings of Rosai-Dorfman disease and to determine association with parvovirus 19. DESIGN: The study is an observational case series of three patients that had atypical ocular presentations of Rosai-Dorfman disease. METHODS: A multicenter, retrospective case series of 3 patients was evaluated for varied ocular complaints, including enlarging epibulbar masses and uveitis. Histologic specimens were examined retrospectively for parvovirus 19 antigen. RESULTS: Patients presented with ocular findings prior to or concurrently with systemic findings, with and without associated lymphadenopathy. Two cases presented with epibulbar masses, one with the mass as the only sign of disease while the other exhibited multinodal involvement with bilateral epibulbar masses and anterior granulomatous inflammation. Parvovirus B19 antibody staining was negative in these cases. The final case exhibited bilateral anterior granulomatous inflammation and choroidal infiltrates. CONCLUSIONS: Ocular findings may be the sole or presenting complaint in Rosai-Dorfman disease prior to recognition of systemic disease and should be considered in the differential diagnosis of epibulbar masses as well as anterior and posterior granulomatous inflammation.

Expression of Sp1 and KLF6 in the developing human cornea.

PURPOSE: To examine the temporal and spatial expression of Sp1 and Krüppel-like factor 6 (KLF6) in the cornea in fetal and adult human eyes. METHODS: Eyes from human fetus (F) of 7, 9, 10, 11, 13, and 27 weeks (w) of gestation, as well as corneas from 11 and 56-day (d)-old children and donors 2, 6, 16, 25, 40, 51, 69, and 83 years (y) of age were obtained. All specimens were fixed in 10% buffered formalin, processed for paraffin sections, and examined for Sp1 and KLF6 expression immunohistochemically. RESULTS: Staining for Sp1 was evident at the earliest F7w time point in the cornea. From F7w to F27w, the moderate to strong Sp1 immunostaining was seen in the nuclei of epithelial and endothelial cells. Staining in keratocytes was also observed. The intensity of Sp1 staining in all layers of the cornea was substantially decreased 11d after birth and remained low thereafter. Positive KLF6 staining was also noted at F7w in all corneal layers. In the epithelium and endothelium, the staining was mostly cytoplasmic throughout the fetal stages. After birth, the KLF6 staining appeared in the nuclei of corneal epithelial cells along with that in the cytoplasm. The intensity of KLF6 staining in the epithelium and endothelium remained relatively constant from E47d to the 83y-old donor cornea. The KLF6 staining in the stroma however was reduced after F27w. CONCLUSIONS: The present study indicates that the expression of Sp1 and KLF6 is developmentally regulated, providing a basis for further investigations on the regulation of the Sp1 and KLF6 gene during the course of corneal development and in corneal diseases such as keratoconus.

Kruppel-like factor 6 (KLF6) affects the promoter activity of the alpha1-proteinase inhibitor gene.

PURPOSE: Keratoconus is a progressive disease that thins and scars the cornea. In keratoconus corneas, levels of degradative enzymes, including lysosomal acid phosphatase (LAP) and cathepsin B, are elevated, and those of inhibitors alpha1-proteinase inhibitor (alpha1-PI) and alpha2-macroglobulin (alpha2-M) are reduced. The present study explored the possible involvement in keratoconus of Krüppel-like factor 6 (KLF6), a transcription factor previously described to be essential for the integrity of the corneal epithelium. The transcript and proteins level of KLF6 and its action in regulating the genes affected in keratoconus were examined in this study. METHODS: Semiquantitative RT-PCR, Western blot analysis, immunofluorescence and in situ hybridization were used to investigate the expression of KLF6 mRNA and protein in normal and keratoconus corneas. Modulation by KLF6 of the promoter activity of alpha1-PI, LAP, cathepsin B, and alpha2-M genes was studied after transient transfection of KLF6 expression plasmid into corneal epithelial cells using promoter-reporter gene assays. Chromatin immunoprecipitation (ChIP) assays were performed to confirm the interactions between KLF6 and promoters of the genes affected in keratoconus. RESULTS: A global increased expression of the transcription factor KLF6 in terms of mRNAs and proteins was observed in total cornea and/or the epithelium in a substantial number of the keratoconus specimens. The promoter activity of the human alpha1-PI gene was suppressed by expression of KLF6 in corneal epithelial cells. The ChIP assay confirmed a physical interaction between KLF6 and the alpha1-PI promoter. CONCLUSIONS: Transcription factor KLF6 downregulates the alpha1-PI gene in corneal epithelial cells and may thereby be involved in keratoconus.