Validation of a Modified National Eye Institute Grading Scale for Corneal Fluorescein Staining.

Purpose: Validation of the novel Lexitas modified NEI scale for use in assessment of corneal fluorescein staining. Patients and Methods: A series of 18 illustrations and 14 clinical photographs depicting varying severity levels of corneal fluorescein staining were assessed by 3 independent examiners. Regions of the cornea were graded for staining severity based on 3 different grading scales: the original NEI staining scale (density-based scoring; 0-3 scale), a structured version of the NEI scale (dot-count scoring; 0-3 scale), and the Lexitas modified NEI staining scale (0-4 scale with half-point increments). Kappa statistics (simple and weighted) were computed to determine intra-examiner image grading repeatability for each examiner over 2 separate assessments. Inter-examiner assessment reliability utilized the scores from the first read of each examiner, and pairs of examiners to compute kappa statistics. Results: Data was analyzed from the scores provided by the examiners from each gradable corneal region on 32 images (18 illustrations and 14 photographs) for a total of 154 corneal regions across the 3 grading scales for each validation run. The mean intra-examiner simple/weighted kappa values using the NEI density, NEI dot count, and the Lexitas modified NEI staining scales were 0.67/0.72, 0.91/0.94, 0.80/0.92 for the graded illustrations, and 0.83/0.88, 0.76/0.85, 0.77/0.88 for the graded photographs, respectively. The mean inter-examiner simple/weighted kappa values using the NEI density, NEI dot count, and the Lexitas modified NEI staining scales were 0.59/0.65, 0.86/0.90, and 0.78/0.91 for the graded illustrations, and 0.80/0.88, 0.84/0.89, 0.69/0.88 for the graded photographs, respectively. Conclusion: The expanded scale of the Lexitas modified NEI staining scale demonstrated a high degree of reliability and repeatability of grading assessments within and across individual examiners, comparing favorably with the original NEI staining scale. A future investigation into the in-office utility of the Lexitas modified NEI staining scale is warranted.

The Safety and Biological Activity of OTT166, a Novel Topical Selective Integrin Inhibitor for the Treatment of Diabetic Eye Disease: A Phase 1b Study.

BACKGROUND AND OBJECTIVES: To evaluate the safety, tolerability, and biological activity of a topical selective integrin inhibitor (OTT166) eyedrop administered BID for diabetic retinopathy (DR) and diabetic macular edema (DME). STUDY DESIGN/MATERIALS AND METHODS: A prospective, multicenter, randomized, double-masked Phase 1b study. Subjects with nonproliferative DR and DME with central subfield thickness (CST) &gt; 325 microns were randomized to OTT166 eyedrops (2.5% or 5%) BID for 28 days. Subjects were followed for an additional 28 days after treatment cessation. RESULTS: Forty-four subjects were enrolled. No drug-related serious adverse events (SAEs) and two drug-related adverse events (AEs) were reported. OTT166 was well-tolerated with no evidence of ocular toxicity. Best-corrected visual acuity (BCVA) remained stable. Mean central retinal thickness (CRT) overall was variable: +12.8/+1.8 microns at Day 28 (end of treatment) and -50.3/+5.5 microns at Day 56 (end of study) for the 2.5% and 5% groups, respectively. Median CRT overall demonstrated consistent reduction by end of study: -39.0/-16.5 microns for the 2.5% and 5% groups, respectively. Median responses were greater in the treatment-naïve group (-41.5/-26.0 microns for the 2.5% and 5% groups, respectively). Thirty-seven percent of 'responder' subjects exhibited a mean reduction in CRT of 46.6 microns on optical coherence tomography (OCT) at end of treatment (Day 28) which persisted to end of the study (Day 56) - mean reduction of 67.4 microns, suggesting a durable effect. CONCLUSION: OTT166 eyedrops were safe, well-tolerated, and demonstrated biological activity in 37% of responders. These results warrant further evaluation of OTT166 eyedrops. <b>[<i>Ophthalmic Surg Lasers Imaging Retina</i> 2022;53:553-560.]</b>.

Inherited Retinal Dystrophy in Southeastern United States: Characterization of South Carolina Patients and Comparative Literature Review.

Inherited retinal dystrophies (IRDs) are a group of rare diseases involving more than 340 genes and a variety of clinical phenotypes that lead to significant visual impairment. The aim of this study is to evaluate the rates and genetic characteristics of IRDs in the southeastern region of the United States (US). A retrospective chart review was performed on 325 patients with a clinical diagnosis of retinal dystrophy. Data including presenting symptoms, visual acuity, retinal exam findings, imaging findings, and genetic test results were compiled and compared to national and international IRD cohorts. The known ethnic groups included White (64%), African American or Black (30%), Hispanic (3%), and Asian (2%). The most prevalent dystrophies identified clinically were non-syndromic retinitis pigmentosa (29.8%), Stargardt disease (8.3%), Usher syndrome (8.3%), cone-rod dystrophy (8.0%), cone dystrophy (4.9%), and Leber congenital amaurosis (4.3%). Of the 101 patients (31.1%) with genetic testing, 54 (53.5%) had causative genetic variants identified. The most common pathogenic genetic variants were USH2A (n = 11), ABCA4 (n = 8), CLN3 (n = 7), and CEP290 (n = 3). Our study provides initial information characterizing IRDs within the diverse population of the southeastern US, which differs from national and international genetic and diagnostic trends with a relatively high proportion of retinitis pigmentosa in our African American or Black population and a relatively high frequency of USH2A pathogenic variants.

Corneal melt in conjunctival intraepithelial neoplasia.

PURPOSE: Report a case of corneal melt in a patient with conjunctival intraepithelial neoplasia (CIN) treated with topical interferon (IFN) alpha-2B. OBSERVATIONS: An 89-year-old man presented with gelatinous paralimbal lesions of the left eye extending onto the cornea with corneal neovascularization extending 5-6 clock hours. Nasally there was mild absence of the terminal vascular loops of the limbal palisades of Vogt and conjunctivalization. Diffuse punctate epithelial erosions were noted. The corneal graft displayed subepithelial and stromal edema. Anterior segment optical coherence tomography detected hyperreflectivity, sectional thickened epithelium, and abrupt transitions from normal to abnormal tissue. The patient was treated with excision of the corneal and conjunctival lesions with cryotherapy to the conjunctival borders. Excisional biopsy revealed CIN Grade 3 and carcinoma in situ of the cornea. Topical IFN alpha-2B four times daily was initiated postoperatively. Two months later, a central epithelial defect developed. The cornea progressively thinned and corneal melt ensued. The patient had several risk factors for corneal melt including neurotrophic cornea, early limbal stem cell deficiency, history of cryotherapy, keratoconjunctivitis sicca, and chronic use of glaucoma medications and steroid medications. CONCLUSIONS: Interferon alpha-2B is an effective first line treatment for CIN with few side effects. It's side effects include punctate epithelial erosions, conjunctival hyperemia, and follicular conjunctivitis. We report a case of pre-existing keratoconjunctivitis sicca, early limbal stem cell deficiency, neurotrophic cornea, and newly diagnosed CIN Grade 3; it was treated with surgical excision, cryotherapy, and topical IFN alpha-2b with development of corneal melt 2 months later. Caution should be taken when using interferon alpha -2b in patients with pre-existing keratoconjunctivitis sicca, neurotrophic cornea, or limbal stem cell deficiency as it could exacerbate these conditions resulting in corneal melt.

Iris melanoma presenting as childhood glaucoma.

PURPOSE: To describe the natural history and management of a rare case of iris melanoma in a pediatric patient. OBSERVATIONS: A Caucasian female presented with left pupillary abnormalities at age 7, progressive iris changes at age 9, and markedly elevated intraocular pressure with advanced optic nerve cupping at 11 years of age. She was found to have a pigmented lesion overlying her iris and invading her angle. Trans-corneal fine needle aspirate biopsy demonstrated malignant melanoma of the iris. The patient subsequently underwent Iodine-125 plaque brachytherapy for the tumor. CONCLUSIONS: and Importance: Early identification and treatment of iris melanoma may be associated with decreased risk of local progression and metastatic disease. Treatment of glaucoma in conjunction with uveal melanoma is complicated by tumor specific considerations, including treatment of the tumor and prevention of metastasis.

Detection of Minimally Visible Recurrent Retinoblastoma by Hand-held Spectral-Domain Optical Coherence Tomography.

A 2-month-old male infant with bilateral familial retinoblastoma was treated with intravenous chemotherapy and focal adjuvant therapy. At 5 months of follow-up, fundus examination and ultrasonography disclosed no recurrence; however, hand-held spectral-domain optical coherence tomography (SD-OCT) demonstrated subclinical recurrence within a previous regression scar. Subsequent treatment led to flat scar. Hand-held SD-OCT can be a useful tool for detection of subclinical recurrent retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2017;54:e6-e8.].

VARIABILITY IN FOVEAL AVASCULAR ZONE AND CAPILLARY DENSITY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MACHINES IN HEALTHY EYES.

PURPOSE: To evaluate the variability in foveal avascular zone (FAZ) and capillary density measurements on optical coherence tomography angiography using Optovue RTVue XR Avanti (OA) (Optovue) and Zeiss Cirrus HD-OCT 5000 (ZC) (Carl Zeiss Meditec). METHODS: In this prospective, comparative case series, parafoveal (3 × 3 mm) optical coherence tomography angiography scans were obtained on healthy volunteers using both the Avanti and Cirrus. The FAZ area and capillary density at the level of both the superficial and deep capillary plexus were measured automatically using the built-in ReVue software (Optovue) with the Avanti as well as manually using ImageJ (National Institutes of Health) with both machines. RESULTS: There were 50 eyes in 25 healthy volunteers included in the analysis. Mean subject age was 33 years and there were 14 women (56%). On optical coherence tomography, mean central macular thickness was significantly greater on OA (259.1 µm) than ZC (257.6 µm, P = 0.0228). On optical coherence tomography angiography, mean superficial and deep plexus FAZ measured 0.2855 mm and 0.3465 mm on Avanti automated (A-A), 0.2739 mm and 0.3637 mm on Avanti manual (A-M), and 0.2657 mm and 0.3993 mm on Cirrus manual (C-M), respectively. There were no statistically significant differences in superficial plexus FAZ measurements between the A-A and A-M (P = 0.4019) or A-A and C-M (P = 0.1336). The A-M measured significantly larger than C-M (P = 0.0396). Deep plexus FAZ measurements were similar on A-A and A-M (P = 0.6299), but both were significantly less compared with C-M (P < 0.0001 for A-A vs. C-M, P = 0.0184 for A-M vs. C-M). Mean superficial and deep plexus capillary densities were 53.6% and 59.3% on A-A, 48.1% and 47.7% on A-M, and 52.5% and 48.1% on C-M, respectively. Superficial plexus capillary density measurements were statistically similar on A-A and C-M (P = 0.0623), but both were significantly higher than A-M (P < 0.0001 for A-A vs. A-M, P < 0.0001 for A-M vs. C-M). However, deep plexus capillary density measurements on A-A were significantly higher than A-M (P < 0.0001) and C-M (P < 0.0001), but A-M and C-M measurements were similar (P = 0.5986). There was no significant difference in all parameters measured in both eyes of one subject using any of the three measuring techniques. CONCLUSION: While measurements taken with the same machine and technique are consistent and reliable between fellow eyes, significant variability exists in FAZ and capillary density measurements among different machines and techniques. Comparison of measurements across machines and techniques should be considered with caution.

IMAGE QUALITY AND ARTIFACTS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Comparison of Pathologic and Paired Fellow Eyes in 65 Patients With Unilateral Choroidal Melanoma Treated With Plaque Radiotherapy.

PURPOSE: To study image quality and artifacts seen on optical coherence tomography angiography (OCTA). METHODS: Sixty-five consecutive patients with unilateral posterior uveal melanoma treated with plaque radiotherapy had OCTA during follow-up. Optical coherence tomography angiography was performed on both the affected and fellow eye. Signal strength and frequency of image artifacts on en face images were compared between affected and fellow eyes. RESULTS: A total of 130 eyes in 65 patients were analyzed, the mean age at time of OCTA was 55 years (median: 56, range: 12-81 years), and 39 (39/65, 60%) were female. Majority of tumors were located in the choroid (62/65, 95%) and extramacular (55/65, 85%). The mean distance to the foveola was 4 mm (median: 3, range: 0-18 mm) and optic nerve was 4 mm (median: 4, range: 0-16 mm). Optical coherence tomography angiography was performed at a mean 46 months after plaque radiotherapy. Most patients had a history of radiation maculopathy or papillopathy in the treated eye at the time of OCTA (46/65, 71%). Overall, 95 eyes (95/130, 73%) had at least one significant artifact on OCTA. The most common major artifacts were loss of focus (71/130, 55%), broad (>5 pixels width and >4 lines) blink lines (48/130, 37%), motion artifact (34/130, 26%), specular dot (33/130, 25%), and edge duplication (10/130, 8%). Statistically, eyes treated with plaque radiotherapy (affected vs. fellow eye) were more likely to have at least one major OCTA artifact (92 vs. 54%, P < 0.001) and, specifically, loss of focus was more frequent (78 vs. 31%, P < 0.001). Multivariate analysis found decreased visual acuity significantly associated with higher incidence of broad blink lines (P = 0.0166) and loss of signal (P < 0.0001), whereas male sex was associated with increased loss of signal (P = 0.0015), and distance to the foveola was related to edge duplication (P = 0.0119). CONCLUSION: Image artifacts on OCTA are commonly encountered and appear to be more frequent in eyes with pathology and poor visual acuity. Recognition of these artifacts might help improve image interpretation and decision making.

Flat choroidal melanoma masquerading as central serous chorioretinopathy.

There are several mimickers of choroidal melanoma. We report a patient with recent family stress who developed blurred vision to 20/50 OD and was found to have unilateral central serous chorioretinopathy and a coincidental choroidal nevus. After 1 year without resolution of the subretinal fluid, the patient was referred for our opinion. On examination, visual acuity was 20/50 in the right eye and 20/20 in the left eye. The left eye was normal. Evaluation of the right eye showed a small, pigmented submacular choroidal lesion measuring 4 mm × 3 mm. Ultrasonography documented an isoechoic mass measuring 1.71 mm in thickness. Optical coherence tomography showed subretinal fluid with shaggy photoreceptors and hyper-reflective material within the subretinal fluid, likely indicative of lipofuscin within macrophages. Autofluorescence revealed orange pigment overlying the lesion. These features were strongly suggestive of small choroidal melanoma with five risk factors for tumor growth. Treatment with Iodine-125 plaque brachytherapy was performed on the patient. The readers should keep in mind that choroidal melanoma can manifest as a tiny choroidal mass with related multimodal imaging features of subretinal fluid and orange pigment.

Dissecting Aortic Aneurysm 55 Years after Diagnosis of Iris Flocculi.

PURPOSE: The aim of this study is to report the clinical features, imaging studies, surgical removal, and pathology of congenital iris flocculi in a patient who developed a life-threatening dissecting aortic aneurysm after 55 years of follow-up. METHODS: Documentation with iris photography was performed from age 18 to 55 years, at which time anterior segment optical coherence tomography (OCT) was performed. At the time of subsequent cataract surgery, the iris flocculi were removed in each eye and submitted for light and electron microscopy. RESULTS: The size and shape of the iris flocculi waxed and waned over the years but caused no visual disturbance. Anterior segment OCT demonstrated clear, round cysts with thin lining and no solid component. At the age of 55, congestive heart failure from a dissecting aortic aneurysm was discovered and surgically repaired. Subsequent bilateral cataract surgery and cyst removal were performed, and the iris flocculi were studied with light and electron microscopy. CONCLUSIONS: Congenital iris flocculi cause little, if any, visual impairment in most cases. However, they are occasionally associated with dissecting aortic aneurysm due to a shared mutation in smooth muscle that affects both the iris and the aorta. Patients with iris flocculi should be monitored periodically for aortic abnormalities.

PARAFOVEAL CAPILLARY DENSITY AFTER PLAQUE RADIOTHERAPY FOR CHOROIDAL MELANOMA: Analysis of Eyes Without Radiation Maculopathy.

PURPOSE: To study the parafoveal capillary density using optical coherence tomography angiography (OCTA) in eyes treated with plaque radiotherapy. RESEARCH DESIGN: Retrospective comparative case series. PARTICIPANTS: Ten patients treated with plaque radiotherapy for choroidal melanoma without evident radiation maculopathy on ophthalmoscopy or optical coherence tomography were imaged with OCTA. MAIN OUTCOME MEASURE: Comparison of the parafoveal capillary density in the superficial and deep capillary plexuses in the irradiated versus fellow nonirradiated eye. RESULTS: Overall, mean patient age was 55 years (median: 57, range: 45-65 years), and majority were white (9/10, 90%) and female (9/10, 90%). No patient had diabetes mellitus, and 2 (2/10, 20%) had controlled systemic hypertension. The melanoma was located in the choroid in all patients (10/10, 100%), with 2 (2/10, 20%) in the macular region. The mean largest basal diameter was 11 mm (12, 6-16 mm), and mean thickness was 5 mm (5, 2-10 mm). Mean radiation dose to the tumor apex was 72 Gy (median: 70 Gy, range: 70-85 Gy). Mean foveolar radiation dose was 53 Gy (median: 35 Gy, range: 14-110 Gy). Mean follow-up duration after plaque radiotherapy was 17 months (median: 16 months, range: 5-39 months). There was no ophthalmoscopic evidence of radiation maculopathy throughout the follow-up in every case. Optical coherence tomography demonstrated normal foveal contour without edema or subretinal fluid in every case. On OCTA, there was no significant difference in signal strength (P = 0.1151), central macular thickness (P = 0.9316), and foveal avascular zone area in the superficial (P = 0.1595), and deep (P = 0.1534) capillary plexuses between the irradiated versus fellow eyes. However, there was a statistically significant decrease in capillary density in the parafoveal superficial (P = 0.0005) and deep (P = 0.0067) plexuses in the irradiated eye. In addition, mean logMAR visual acuity was 0.2 (0.1, 0.0-0.5) (Snellen equivalent 20/32) in the irradiated eye and 0.0 (0.0, range: 0.0-0.1) (Snellen equivalent 20/20) in the fellow eye (P = 0.0252). CONCLUSION: Optical coherence tomography angiography allows qualitative and quantitative analysis of parafoveal capillary density. After plaque radiotherapy for choroidal melanoma, in eyes with normal macular features on ophthalmoscopy and optical coherence tomography, there is a statistically significant decrease in parafoveal capillary density and logMAR visual acuity in irradiated eyes compared with fellow eyes. These subclinical ischemic findings represent the commencement of radiation maculopathy.

Unilateral Retinoblastoma Managed With Intravenous Chemotherapy Versus Intra-Arterial Chemotherapy. Outcomes Based on the International Classification of Retinoblastoma.

PURPOSE: The objective of this study was to compare outcomes after intravenous chemotherapy (IVC) versus intra-arterial chemotherapy (IAC) for unilateral retinoblastoma. DESIGN: A retrospective comparative interventional case series. METHODS: Patients with unilateral retinoblastoma managed with either IVC using vincristine, etoposide, and carboplatin or IAC using melphalan with or without topotecan with a minimum of 1-year follow-up were compared. The primary outcome measure was globe salvage. RESULTS: Of 91 patients with unilateral retinoblastoma, IVC was employed in 42 (46%) cases and IAC in 49 (54%). By comparison (IVC vs IAC), patients in the IAC group had greater mean tumor diameter (14 vs 18 mm, P < 0.001) and thickness (7 vs 10 mm, P = 0.001), greater percentage with active vitreous seeds (29% vs 55%, P = 0.01), and greater total retinal detachment (10% vs 43%, P < 0.001). There were no cases of group A in either treatment arm. Globe salvage was not significantly different in groups B, C, or E, but there was significantly improved globe salvage with IAC for group D (48% vs 91%, P = 0.004). Control was significantly better with IAC for solid tumor (62% vs 92%, P = 0.002), subretinal seeds (31% vs 86%, P = 0.006), and vitreous seeds (25% vs 74%, P = 0.006). There were no patients with pinealoblastoma, second cancer, metastasis, or death in either group. CONCLUSIONS: For unilateral retinoblastoma, IAC provided significantly superior globe salvage compared with IVC for group D eyes. In addition, IAC provided significantly superior control for solid tumor, subretinal seeds, and vitreous seeds.

CORRELATION OF FOVEAL AVASCULAR ZONE SIZE WITH FOVEAL MORPHOLOGY IN NORMAL EYES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To analyze the foveal avascular zone (FAZ) in normal eyes using optical coherence tomography angiography. METHODS: Prospective noncomparative case series. The parafoveal region of 70 eyes from 67 healthy subjects was imaged using optical coherence tomography angiography to visualize the superficial and deep capillary plexuses and correlated with standard macular volume scans using spectral domain optical coherence tomography to determine foveal morphology. RESULTS: In all 70 eyes imaged, 2 vascular plexuses could be detected within the retina: a superficial plexus within the ganglion cell layer and a deep plexus within the inner nuclear layer. A measurable FAZ was visualized in both plexuses in all imaged eyes. The FAZ area was variable in the study population with a mean of 0.266 mm² ± 0.097 mm² in the superficial plexus (range: 0.071 mm²-0.527 mm²) and a mean of 0.495 mm² ± 0.227 mm² in the deep plexus (range: 0.160 mm²-0.795 mm²). The FAZ area was significantly larger in the deep plexus (P < 0.0001) compared with superficial plexus. The FAZ area in both plexuses correlated inversely with central macular thickness and central macular volume (P < 0.0001). No significant correlation was found between superficial plexus FAZ area and age (P = 0.55) or sex (P = 0.34). In the same manner, no significant correlation was found between deep plexus FAZ area and age (P = 0.13) or sex (P = 0.13). CONCLUSION: Optical coherence tomography angiography provides a noninvasive method to visualize and measure the superficial and deep plexus FAZ in a normal population. The FAZ can vary in size and shape, with the FAZ area significantly larger in the deep compared with the superficial plexus. Both superficial and deep FAZ area correlate inversely with foveal thickness and volume.

Mini- and Maxi-peaks of Combined Hamartoma on Enhanced Depth Imaging Optical Coherence Tomography.

A 17-year-old asymptomatic boy with a referral diagnosis of "macular gliosis" was found to have a combined hamartoma of the retina and retinal pigment epithelium. Enhanced depth imaging optical coherence tomography showed characteristic features of mini- and maxi-peaks from vitreoretinal traction.

Multimodal imaging for detection of clinically inapparent diffuse iris juvenile xanthogranuloma.

A 6-month-old female infant was referred following three episodes of spontaneous hyphema. Iris juvenile xanthogranuloma was suspected but not clinically visible. Multimodal imaging with fluorescein angiography, anterior segment optical coherence tomography, and ultrasound biomicroscopy were used to detect the flat, transparent lesion and cytopathology confirmed juvenile xanthogranuloma.

Esophageal adenocarcinoma and urothelial carcinoma orbital metastases masquerading as infection.

Orbital metastases can masquerade as other orbital processes. We present two cases of orbital metastases, the first being the first reported adenocarcinoma of the esophagus presenting as an orbital metastasis prior to the primary being known, and the other as the first urothelial carcinoma to present as orbital cellulitis. The first patient presented with left upper eyelid pain. CT scan identified a superolateral subperiosteal fluid collection without concomitant sinus disease, which was drained in the operating room. Two weeks later repeat CT scan showed recurrent orbital subperiosteal fluid. It was drained and a biopsy showed necrotic adenocarcinoma. The second case presented with a painless right proptosis, decreased vision, and globally decreased ocular motility 3 days after bladder resection for urothelial carcinoma. CT scan demonstrated pan sinusitis with a soft tissue mass in the apex of the right orbit with extension through the superior orbital fissure. After no improvement on antibiotics endoscopic drainage was performed. Pathology revealed metastatic urothelial carcinoma within the orbital fat.