Capillary density and caliber as assessed by optical coherence tomography angiography may be significant predictors of diabetic retinopathy severity.

PURPOSE: To validate retinal capillary density and caliber associations with diabetic retinopathy (DR) severity in different clinical settings. METHODS: This cross-sectional study assessed retinal capillary density and caliber in the superficial retinal layer of 3-mm OCTA scans centered on the fovea. Images were collected from non-diabetic controls and subjects with mild or referable DR (defined DR worse than mild DR) between February 2016 and December 2019 at secondary and tertiary eye care centers. Vessel Skeleton Density (VSD), a measure of capillary density, and Vessel Diameter Index (VDI), a measure of vascular caliber, were calculated from these images. Discriminatory performance of VSD and VDI was evaluated using multivariable logistic regression models predicting DR severity with adjustments for sex, hypertension, and hyperlipidemia. Area under the curve (AUC) was estimated. Model performance was evaluated in two different cohorts. RESULTS: This study included 594 eyes from 385 subjects. Cohort 1 was a training cohort of 509 eyes including 159 control, 155 mild non-proliferative DR (NPDR) and 195 referable DR eyes. Cohort 2 was a validation cohort consisting of 85 eyes including 16 mild NPDR and 69 referable DR eyes. In Cohort 1, addition of VSD and VDI to a model using only demographic data significantly improved the model's AUC for discrimination of eyes with any DR severity from controls (0.91 [95% CI, 0.88-0.93] versus 0.80 [95% CI, 0.76-0.83], p < 0.001) and eyes with referable DR from mild NPDR (0.90 [95% CI, 0.86-0.93] versus 0.69 [95% CI, 0.64-0.75], p < 0.001). The transportability of this regression model was excellent when implemented in Cohort 2 for the referable DR versus mild NPDR comparison. The odds ratio of having any DR compared to control subjects, and referable DR compared to mild DR decreased by 15% (95% CI: 12-18%), and 13% (95% CI: 10-15%), respectively, for every 0.001 unit increase in VSD after adjusting for comorbidities. CONCLUSION: OCTA-derived capillary density has real world clinical value for rapidly assessing DR severity.

Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle Aspiration Biopsy Specimens of Uveal Melanoma.

PURPOSE: The aim of this paper was to assess the concordance between results of DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing intraoperative fine-needle aspiration biopsy (FNAB) for metastatic prognostication during brachytherapy. METHODS: We retrospectively reviewed consecutive patients diagnosed with posterior uveal melanoma who underwent intraoperative FNAB prior to placement of an iodine-125 radioactive plaque between 2012 and 2014. Two cohorts of patients were identified: Cohort 1 - tumors in which both GEP and FISH results were obtained, and Cohort 2 - tumors in which both GEP and MLPA results were obtained. RESULTS: Forty-four patients were identified for Cohort 1. FISH and GEP results were discordant in 7 tumors (15.9%). Forty-three patients were identified for Cohort 2. MLPA and GEP were discordant in 7 tumors (16.3%). CONCLUSIONS: Discordance between GEP and chromosome 3 status by FISH and MLPA occurred in our series at a rate of 15.9 and 16.3%, respectively. Caution must be advised when counseling a patient with a good-prognosis GEP "Class 1" result that the uveal tumor may actually harbor monosomy 3, which is associated with a poor prognosis for metastasis in nearly 20% of the patients.

CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

PURPOSE: To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. METHODS: Clinical examination and multimodal imaging of the case. RESULTS: A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. CONCLUSION: The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

Variable Results for Uveal Melanoma-Specific Gene Expression Profile Prognostic Test in Choroidal Metastasis.

IMPORTANCE: We report our experience with uveal melanoma-specific gene expression profile (GEP) testing on a series of choroidal metastatic tumors confirmed by cytopathology so that clinicians may be aware that receiving a class 1 or class 2 test result in nonmelanoma is possible. OBSERVATIONS: Retrospective review of all cytopathology and DecisionDx-UM GEP reports between January 2012 to December 2014 from intraoperative fine-needle aspiration biopsy of choroidal tumors undergoing brachytherapy. Four patients were identified to have cytopathology consistent with a nonmelanoma primary. All 4 patients presented with a unilateral, single choroidal tumor, which was treated with iodine-125 brachytherapy and underwent intraoperative fine-needle aspiration biopsy for cytopathology and uveal melanoma-specific GEP testing for molecular prognostication. Gene expression profile testing of the choroidal tumor in each patient revealed class 1A in 3 patients and class 2 in 1 patient. CONCLUSIONS AND RELEVANCE: DecisionDx-UM GEP may be a helpful test for molecular prognostication in patients with uveal melanoma; however, class 1 and class 2 test results are indeed possible in the setting of a nonmelanoma malignancy. We recommend that cytopathology and/or other melanoma-specific testing be performed in all cases of suspected choroidal melanoma because GEP with this assay is unable to rule out the diagnosis of a choroidal melanoma.

Spontaneous dislocation of fluocinolone acetonide implant pellets from their suture struts.

PURPOSE: To characterize spontaneous dislocation of the fluocinolone acetonide sustained release implant (Retisert; Bausch & Lomb) drug pellet from its strut. DESIGN: Retrospective, observational case series. METHODS: The medical records of 224 patients in whom 407 fluocinolone acetonide implants were placed by either of 2 surgeons between 1998 and 2012 were reviewed for drug pellet-suture strut separation, observed before surgery in clinic or occurring at the time of implant replacement. RESULTS: Seventeen (4.2%) of 407 drug pellets spontaneously dislocated away from the suture strut at a mean postimplantation time of 77.4 months (range, 33 to 132 months). The rate of spontaneous dislocation increased from 1 dislocation per 262 person years (95% confidence interval, 1 per 1269 to 1 per 89.6 person-years) before 60 months to 1 dislocation per 13.3 person-years (95% confidence interval, 1 per 24.4 to 1 per 7.9 person-years) afterward. Fourteen of 17 dislocated pellets were removed surgically. Of 77 exchanged fluocinolone acetonide implants without dislocated pellets, 11 (14.2%) pellets had separated, but not dislocated away, from the strut; time to exchange of dislocated or dissociated pellets was significantly longer than time to exchange of intact fluocinolone acetonide implants (70.5 vs 44.9 months; P < .001). CONCLUSIONS: The fluocinolone acetonide drug pellet can dislocate spontaneously from the suture strut as a late event that typically occurs after 3 years. Pellets also may be dissociated from the strut without dislocation, when separation occurs at the time of surgical replacement. Removal of the dislocated pellet can be achieved safely. Time was the major risk factor identified for both events.

Clinical course and origin of epithelium in cases of epithelial downgrowth after Descemet stripping automated endothelial keratoplasty.

PURPOSE: The aim of this study was to report a case series of epithelial downgrowth associated with Descemet stripping automated endothelial keratoplasty (DSAEK) and to explore the origin of the anterior chamber corneal epithelium. METHODS: This is a case series and literature review. RESULTS: Three histopathologically confirmed cases of epithelial downgrowth after DSAEK were identified. All cases were treated with argon laser ablation, intracameral 5-fluorouracil, and intraocular surgery. Recurrent epithelial downgrowth occurred in 2 of 3 cases. Fluorescent in situ hybridization analysis with fluorescent probes for X and Y chromosomes was used to analyze epithelial downgrowth tissues in all cases. All 3 cases were consistent with donor tissue origin of epithelial downgrowth tissue. However, this could only be confirmed in 1 case. The donor and the recipient were the same sex in 2 cases; thus, no definitive conclusion was possible in these patients. CONCLUSIONS: There have been multiple reports of epithelial downgrowth after DSAEK. We include additional evidence to support the role of donor tissue corneal cells as the source of epithelium in some of these cases. It is surprising that donor tissue would be tolerated immunologically by the patient in these cases. We propose that tolerance for donor epithelium may be mediated through anterior chamber-associated immune deviation.

Vitamin D deficiency in neovascular versus nonneovascular age-related macular degeneration.

PURPOSE: To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. METHODS: Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. RESULTS: Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18-0.68) odds ratio for NVAMD. CONCLUSION: This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD.

Intravitreal alemtuzumab penetrates full-thickness retina in rabbit eyes.

PURPOSE: The purpose of this study was to assess whether alemtuzamab, a large antibody of 150 kDa, would be able to penetrate through the full-thickness retina of Dutch-belted rabbits. METHODS: Four Dutch-belted rabbits had intravitreal injections of alemtuzumab (1.5 mg in 0.05 mL). One rabbit each was killed at Day 1, Day 8, Day 15, and Day 29. The eyes were examined under frozen section and graded by immunostaining techniques for the degree of penetration of alemtuzumab into the retina. The degree of retinal staining was graded from 0 (no stain) to 4+ (marked stain). RESULTS: All study eyes showed antibody staining of the full-thickness retina as follows: 4+ at Day 1, 4+ at Day 8, 3+ at Day 15, and 2+ at Day 29. CONCLUSION: A 1.5-mg intravitreal dose of alemtuzumab was able to penetrate full-thickness retina throughout the full 29-day course of the study. Retinal toxicity studies are required before clinical use.

Anti-cyclic citrullinated peptide, rheumatoid factor, and ocular symptoms typical of rheumatoid arthritis.

PURPOSE: To correlate the presence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) with ocular symptoms typical of rheumatoid arthritis (RA). METHODS: The records of 451 patients who had been examined by an ophthalmologist and tested for anti-CCP antibodies over a 3-year period at the Mayo Clinic were reviewed. Records of 255 patients with titers of anti-CCP and RF were analyzed for ocular surface and inflammatory disease associated with ocular RA. RESULTS: Of the 33 anti-CCP+/RF+ patients, all were diagnosed with RA; ocular surface disease was present in 11 (33%) and inflammatory disease in 7 (21%). Of the 17 anti-CCP-/RF+ patients, 4 were diagnosed with an unspecified inflammatory arthritis and 1 with rheumatoid arthritis; a separate 5 (29%) had ocular surface disease. Out of 5 anti-CCP+/RF- patients, 3 were diagnosed with RA but none had ocular symptoms. Out of 200 anti-CCP-/RF- patients, 32 (16%) had ocular surface disease and 2 (1%) had ocular inflammation. Of the 74 patients diagnosed with any form of inflammatory arthritis, anti-CCP+/RF+ patients had more and worse inflammatory ocular RA disease compared to the other groups. CONCLUSIONS: Patients who were both anti-CCP and RF positive tended to have more and worse ocular disease. In patients diagnosed with an inflammatory arthritis, the presence of anti-CCP antibodies and RF provides useful information to ophthalmologists for identifying patients most at risk for inflammatory ocular disease.

Outcomes of epithelial debridement for anterior basement membrane dystrophy.

PURPOSE: To evaluate the outcomes of simple mechanical debridement for the management of anterior basement membrane dystrophy (ABMD) in a cohort of patients treated primarily for visual symptoms. DESIGN: Retrospective, observational case series. METHODS: setting: Single center. study population: Seventy-four eyes of 55 patients treated with mechanical epithelial debridement over a 15-year period. observation procedures: We recorded symptoms, pre- and postoperative best-corrected visual acuity (BCVA), surgical technique, complications, and evidence of disease recurrence. main outcome measures: Mean best-corrected logMAR acuity and refractive errors, compared by using paired t tests or Wilcoxon signed-rank tests. Interval to recurrence of ABMD was determined by using Kaplan-Meier estimates. RESULTS: Mean patient age was 74 years, and 80% were female. Visual difficulty was reported by the patient before the procedure in 61 eyes (82%), and erosion symptoms alone were noted before the procedure in the remaining 13 eyes. Mean BCVA improved from 20/44 before surgery to 20/30 (P = .0001) at the early follow-up visit and 20/33 (P = .0001) at the last follow-up (mean = 33 months). The mean refractive spherical equivalent changed -0.6 diopters (range, -4.75 to +2.0 diopters). No infections or persistent epithelial defects occurred. The most common postoperative complication was subepithelial haze, occurring in 19 eyes (26%). The five-year cumulative probability of recurrence of ABMD was 44.7%. CONCLUSIONS: Our results with this simple technique are comparable to outcomes reported with other procedures used to treat ABMD. We recommend manual debridement as an effective option for ABMD affecting visual acuity.