Isolated Vitreous Metastasis in a Patient with an ALK Positive Lung Cancer Treated with Lorlatinib.

PURPOSE: To describe the ocular clinical and imaging findings of a patient with isolated vitreous metastasis, confirmed by vitreous biopsy, from an anaplastic lymphoma kinase (ALK) positive metastatic lung cancer. METHODS: case report. RESULTS: A 47-year-old female with a history of metastatic ALK positive lung cancer was referred by her oncologist due to unilateral blurred vision over 4 weeks. The fundus examination showed vitreous opacities with clumps of non-pigmented cells, without vasculitis or retinitis while optical coherence tomography (OCT) showed hyper-reflective deposits on the inner retinal surface with no retinal involvement. Diagnostic vitrectomy revealed neoplastic cells with ALK mutation. CONCLUSION: This is the first report that documents a case of isolated vitreous metastasis from ALK positive lung carcer in a patient under targeted therapy to treat metastatic lung cancer. We emphasize the importance of multimodal imaging, diagnostic vitrectomy, and a pathologist's cooperation to provide essential information about diagnosis and effective treatment.

Atypical unilateral exudative retinal detachment in a child affected by tuberous sclerosis.

INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare hereditary phakomatosis. The clinical features can include benign growths in the central nervous system, tumors of various visceral organs, and retinal or optic disc astrocytic hamartomas in the nerve fiber layer. Here we present the case of a child with known TSC developing Coats-like manifestations. CASE DESCRIPTION: A 22-month-old girl with known TSC and retinal hamartoma followed since birth presented for the development of exotropia and leukocoria in the left eye. Fundus examination of the left eye showed blurred optic disc, macular star, and yellow retinal exudation in the temporal area. In addition, the left eye showed marked retinal vascular tortuosity and telangiectasias. The patient underwent brain and orbit magnetic resonance imaging, revealing heterotopic gray matter nodulations along ependyma of both lateral ventricles, with partial calcification, and a posterior flattening of the left eye. CONCLUSION: This report shows a rare case of Coats-like disease in a child with tuberous sclerosis. In case of presence of Coats' manifestations associated with atypical retinal or systemic findings, genetic diseases should be considered in the differential diagnosis.

The majority of autosomal recessive nanophthalmos and posterior microphthalmia can be attributed to biallelic sequence and structural variants in MFRP and PRSS56.

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from different ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), five of which are novel including a deletion spanning the 5' untranslated region and the first coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identified in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the first MFRP genomic rearrangement, offering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Benign Yellow Dot Maculopathy: A New Macular Phenotype.

PURPOSE: To describe a novel macular phenotype that is associated with normal visual function. DESIGN: Retrospective, observational case series. PARTICIPANTS: Thirty-six affected individuals from 23 unrelated families. METHODS: This was a retrospective study of patients who had a characteristic macular phenotype. Subjects underwent a full ocular examination, electrophysiologic studies, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence imaging. Genomic analyses were performed using haplotype sharing analysis and whole-exome sequencing. MAIN OUTCOME MEASURES: Visual acuity, retinal features, electroretinography, and whole-exome sequencing. RESULTS: Twenty-six of 36 subjects were female. The median age of subjects at presentation was 15 years (range, 5-59 years). The majority of subjects were asymptomatic and presented after a routine eye examination (22/36 subjects) or after screening because of a positive family history (13/36 subjects) or by another ophthalmologist (1/36 subjects). Of the 3 symptomatic subjects, 2 had reduced visual acuity secondary to nonorganic visual loss and bilateral ametropic amblyopia with strabismus. Visual acuity was 0.18 logarithm of the minimum angle of resolution (logMAR) or better in 30 of 33 subjects. Color vision was normal in all subjects tested, except for the subject with nonorganic visual loss. All subjects had bilateral symmetric multiple yellow dots at the macula. In the majority of subjects, these were evenly distributed throughout the fovea, but in 9 subjects they were concentrated in the nasal parafoveal area. The dots were hyperautofluorescent on fundus autofluorescence imaging. The OCT imaging was generally normal, but in 6 subjects subtle irregularities at the inner segment ellipsoid band were seen. Electrophysiologic studies identified normal macular function in 17 of 19 subjects and normal full-field retinal function in all subjects. Whole-exome analysis across 3 unrelated families found no pathogenic variants in known macular dystrophy genes. Haplotype sharing analysis in 1 family excluded linkage with the North Carolina macular dystrophy (MCDR1) locus. CONCLUSIONS: A new retinal phenotype is described, which is characterized by bilateral multiple early-onset yellow dots at the macula. Visual function is normal, and the condition is nonprogressive. In familial cases, the phenotype seems to be inherited in an autosomal dominant manner, but a causative gene is yet to be ascertained.

Intraoperative fluorescein angiography-guided treatment in children with early Coats' disease.

PURPOSE: To review the anatomic and visual outcomes of a series of children diagnosed with Coats' disease and treated on the basis of intraoperative fluorescein angiography (FA) findings. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-five children 2 to 15 years of age diagnosed with early Coats' disease and treated after intraoperative FA. METHODS: Retrospective review of patients who underwent treatment for stage 2 Coats' disease in a tertiary center in the United Kingdom between 2007 and 2012. The children underwent treatment to the telangiectatic vessels and associated areas of retinal nonperfusion identified on intraoperative FA performed with a wide-angle retinal camera (RetCam II). MAIN OUTCOME MEASURES: Anatomic and structural assessment of the retina after treatment, visual acuity (VA), and complications related to treatment. RESULTS: Twenty children with Coats' disease who underwent intraoperative RetCam FA and retinal ablative treatment and who had more than 3 months of follow-up were identified from clinical records. All had unilateral disease. Six eyes were classified as stage 2a, and 14 eyes were classified as stage 2b. The median duration of follow-up was 21 months (mean, 26 months). Fifteen eyes needed 1 treatment to stabilize the disease, and 5 eyes needed a second treatment. None of the patients demonstrated progression of the disease to a more severe stage. Twelve eyes had a final VA of 0.4 logarithm of the minimum angle of resolution (logMAR) or better, 6 patients had VA between 0.4 and 1.0 logMAR, and 2 patients had VA worse than 1.0 logMAR. CONCLUSIONS: The treatment of retinal telangiectasia and areas of retinal nonperfusion identified by wide-angle intraoperative FA in children with stage 2 Coats' disease led to good anatomic outcome, with preservation of VA in most cases.

Diagnostic validity of optic disc and retinal nerve fiber layer evaluations in detecting structural changes after optic neuritis.

PURPOSE: To assess the diagnostic validity of morphometric examination of the optic disc and retinal nerve fiber layer (RNFL) thickness to detect permanent structural changes after retrobulbar optic neuritis (ON). DESIGN: Evaluation of a diagnostic test. PARTICIPANTS: Twenty-five patients with a history of retrobulbar ON and 29 disease-free controls. METHODS: The optic discs were evaluated by means of confocal scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph [HRT III]), and RNFL thickness by means of scanning laser polarimetry (GDx), and optical coherence tomography (OCT). Vision function was assessed in all subjects by testing visual acuity, contrast sensitivity, color vision, visual field (VF), and visual evoked potentials (VEPs). Statistical comparisons were made between the affected (ON) and unaffected eyes (non-ON) of the patients with ON, and between these eyes and control eyes (Mann-Whitney test and Wilcoxon's test). Receiver operating characteristic (ROC) curves, and sensitivity and specificity in discriminating ON from control eyes, were calculated for the significant parameters. Correlations between the tests were calculated by means of Spearman's correlation coefficient. MAIN OUTCOME MEASURES: We compared OCT, GDx, HRT, and visual testing results in ON eyes versus control eyes. RESULTS: All of the visual function test parameters and RNFL thickness (GDx and OCT) were significantly different between the ON eyes and both the non-ON and control eyes (P<0.01), and there were significant differences in some GDx parameters between the non-ON and control eyes. There were no significant differences in the HRT parameters. The ROC curves indicated that the greatest diagnostic validity was associated with the GDx nerve fiber indicator (AUC, 0.92; sensitivity, 0.80; specificity, 0.97 using a cutoff point of 20.5 between ON and non-ON eyes), and OCT temporal thickness (AUC, 0.92; sensitivity, 0.72; specificity, 0.95 using a cutoff point of 51.5 microm). CONCLUSIONS: When investigating permanent damage after ON, RNFL thickness is a promising biomarker. The GDx and OCT are reliable, noninvasive, user-friendly devices; both show good diagnostic validity and good correlations with functional tests in discriminating affected from unaffected eyes. Retinal nerve fiber layer thinning in non-ON eyes should be further studied as a possible subclinical indicator of disease.