Uncommon fundus presentation of Koolen-De Vries Syndrome in a young boy.

INTRODUCTION: Koleen-De Vries syndrome (KDVS) is a rare genetic condition characterized by typical facial features, intellectual disability, cardiac and renal diseases, and ophthalmic manifestations. The syndrome is known to be caused by a microdeletion in the 17q21.31 region, involving multiple genes, including the KANSL1 gene. CASE PRESENTATION: We present the case of a 9-year-old boy with no family history of ophthalmic syndromes. The patient exhibited bilateral hypopigmented iris and unilateral choroidal and retinal pigment epithelium (RPE) hypopigmentation. DISCUSSION: The presence of ophthalmic manifestations, such as bilateral hypopigmented iris and unilateral choroidal and RPE hypopigmentation, in a patient with KDVS adds to the clinical spectrum of this syndrome. Although the exact mechanism underlying these ocular findings is not yet fully understood, the microdeletion in the 17q21.31 region, which includes the KANSL1 gene, is likely to play a role. CONCLUSION: This case highlights the importance of considering ophthalmic manifestations in individuals diagnosed with Koleen-De Vries syndrome. Further research is needed to better understand the pathogenesis and clinical implications of these ocular findings.

Novel retinal findings in a patient with Autosomal recessive Cutis Laxa type 2A.

PURPOSE: To report a case of Autosomal recessive Cutis Laxa type 2A with novel retinal findings. METHODS: Case Report. RESULTS: 22-year-old female patient presented with a longstanding history of reduced visual acuity in her right eye. She has generalized redundant skin, downslanting of palpebral fissures, and long philtrum. Ophthalmic examination showed ptosis in her right eye and visual acuity of 20/2000 in the right eye and 20/30p in the left eye. Funduscopic examination showed a round macular scar lesion in the right eye macula and a chorioretinal scar superonasally in the left eye. Multimodal imaging showed macular atrophy in the right eye with speckled hypoautoflorescence of the described lesions. Genetic testing showed a homozygous splice acceptor variant of the ATP6V0A2 gene. CONCLUSIONS: The natural history of the presented pigmentary lesions is not known and further follow up is needed to assess any progressive nature. Our case adds to the variability of ophthalmic manifestations reported in ARCL2A and therefore to the importance of regular ophthalmic surveillance in patients with Cutis Laxa.

Choroidal neo-vascular membrane in a paediatric optic disc pit: A case report.

Purpose: To report a paediatric patient with unilateral optic nerve pit found to have choroidal neo-vascular membrane in the same eye. Observation: An 8-year old girl known to have a unilateral optic nerve pit presented with exotropia of the right eye. On examination, her vision was 20/40; sub-retinal haemorrhage was noted on clinical fundus exam and a sub retinal vascular net was confirmed on optical coherence tomography angiography. Conclusion and importance: The unusual finding of a choroidal neo-vascular membrane in a known optic nerve pit case represents a new finding of a possible complication. Patients with optic nerve pit may be considered as candidates for OCT-angiography for further diagnosis and proper treatment leading to improved vision, care and prognosis.

Retinal ultra-wide-field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy.

PURPOSE: To compare ultra-wide-field colour fundus imaging (UWFI) to dilated fundus examination (DFE) for the screening of sickle cell retinopathy (SCR). DESIGN: This study is a prospective, blinded, multicentre case series. PARTICIPANTS: This study included two groups: an adult group (n=268 eyes) and a paediatric group (n=168 eyes). Sickle cell disease (SCD) types included haemoglobin S homozygous (HbSS), haemoglobin S and C (HbSC) and Hb S with ß-thalassaemia (HbSß-Thal). METHODS: Participants underwent DFE and UWFI. Each eye received three independent grades (1-4), documented by three graders: clinical grader, image grader 1 and image grader 2. Three clinically relevant diagnostic thresholds were determined. Based on these thresholds, the sensitivity, specificity, positive predictive value and negative predictive value for all three graders were calculated relative to each other as reference tests. RESULTS: HbSC was associated with the most advanced SCR grades. When compared to the clinical grader, image grader 1 and image grader 2 consistently detected more SCR and higher SCR grades in both adult and paediatric groups. In both groups, image grader 1 and image grader 2 identified twice as many cases of capillary occlusion/anastomosis than clinical grader. To detect the presence of any proliferative SCR, image grader 1 and image grader 2 had a sensitivity of 82%, 71% in the paediatrics group and 90% and 72% in the adult group. The clinical grader sensitivity was 52% in the paediatrics group and 53% in the adult group. CONCLUSION: The UWFI is a sensitive tool to screen for SCR. It is superior to DFE in detecting capillary occlusion or anastomosis.

Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt Disease Using En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography.

PURPOSE: This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD). DESIGN: Prospective cross-sectional study. METHODS: This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated. RESULTS: The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P < 0.0001) by a 1.6:1 ratio (r2 = 0.90). CCVD within regions of matched degeneration (85.6% ± 2.7%; P < 0.0001), isolated IS/OS junction loss (93.6% ± 1.0%; P = 0.0011), and isolated RPE atrophy (94.1% ± 1.1%; P = 0.0065) were all significantly lower than normal (99.0% ± 0.17%). There was a trend for CCVD within intact areas (97.6% ± 0.38%) to decline as the area diminished (r = 0.68). CONCLUSIONS: Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. METHODS: This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). RESULTS: The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. CONCLUSION: Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.

Longitudinal ophthalmic findings in a child with Helsmoortel-Van der Aa Syndrome.

PURPOSE: We present the first detailed ophthalmic description of a child with Helsmoortel-Van der Aa Syndrome (HVDAS), including longitudinal follow-up and analysis. OBSERVATIONS: After extensive workup, a young child with poor visual behavior, hypotonic cerebral palsy, intellectual disability, and global developmental delay was found to have a heterozygous de novo mutation in the ADNP gene and diagnosed with HVDAS. Ophthalmic findings were remarkable for progressive nystagmus, macular pigment mottling, mild foveal hypoplasia with abnormal macular laminations, persistent rod dysfunction with electronegative waveform, and progressive cone degeneration. CONCLUSIONS AND IMPORTANCE: Patients with HVDAS are known to have abnormal visual behavior due to refractive or cortical impairment. However, we present the first description, to our knowledge, of an association with retinal mal-development and degeneration. Thus, patients with HVDAS should be referred for ophthalmic genetics evaluation, and HVDAS should be on the differential diagnosis for young children with global developmental delay who present with nystagmus, rod and cone dysfunction with electronegative waveform, and relative lack of severe structural degeneration on optical coherence tomography.

SCLERAL PITS IN CHOROIDEREMIA: Implications for Retinal Gene Therapy.

PURPOSE: We report a novel finding on spectral domain optical coherence tomography in patients with choroideremia, which we describe as scleral pits (SCPs). METHODS: Cross-sectional observational case series of 36 patients with choroideremia, who underwent ophthalmic examination and multimodal imaging, including optical coherence tomography of the macula. Optical coherence tomography images were reviewed for SCP, which were defined as discrete tracts of hyporeflectivity that traverse the sclera with or without the involvement of Bruch membrane, retinal pigment epithelium, and retina. Unpaired two-tailed t-test with Welch correction was used for statistical analysis. RESULTS: Of the 36 patients, 19 had SCP in at least one eye. Scleral pits were confined to areas of advanced chorioretinal degeneration and never involved the foveola. Type 1 SCP affected only the sclera, whereas Type 2 SCP also involved the Bruch membrane and the retinal pigment epithelium. Type 3 SCP additionally had a full-thickness retinal defect. Patients with SCP were significantly older (51 ± 2 vs. 33 ± 4 years; P < 0.05) and had lower best-corrected visual acuity (20/160 vs. 20/30 or 0.9 ± 0.2 vs. 0.2 ± 0.07 logarithm of the minimum angle of resolution; P < 0.05) than patients without SCP. Patients with SCP had a greater myopic refractive error compared with patients without SCP (-2.6 ± 0.5 vs. -0.3 ± 0.5D; P < 0.05), but there was no significant correlation between the number of SCPs with refraction. Short posterior ciliary arteries were observed to enter the eye through one Type 3 SCP. CONCLUSION: Scleral pits are, to the best of our knowledge, a novel optical coherence tomography finding in advanced choroideremia that likely represents the abnormal juxtaposition of penetrating short posterior ciliary arteries with the retina.

Visual Function and Central Retinal Structure in Choroideremia.

PURPOSE: To define the clinical phenotype of a cohort of patients affected with choroideremia. METHODS: A retrospective study of patients with choroideremia included two centers. Data collected included age, visual acuity, refractive error, color vision, kinetic perimetry, optical coherence tomography (OCT), and genotype information. RESULTS: Sixty male participants were recruited. Genotype information was available for 58 cases, and nonsense mutations were most commonly observed. Eight novel mutations were identified including a missense mutation. The mean age at the first visit was 30.1 years (range, 5-65 years) and thirty-seven patients (61%) had more than one visit with a mean follow-up period of 10.3 years (range, 1-23 years). Visual acuity was not associated with age for patients younger than 30 years (P = 0.46) but significantly associated with age for the age group above 30 years (P < 0.0001). Central retinal thickness was significantly associated with visual acuity (P = 0.03) and with age (P = 0.0014). The extent of visual field documented by kinetic perimetry showed a negative correlation with age to tested stimuli; the smallest target used (I-4e) showed the earliest and most rapid deterioration below the age of 20 years (P = 0.0032). Color vision was abnormal in 46.7% of cases (mean age, 36.3 years; range, 18-61 years), which was associated with older age (P = 0.0039). Central OCT images were abnormal in all cases, as early as age 10 years. Outer retinal tubulations were observed in all but five patients. No genotype-phenotype correlation was observed. CONCLUSIONS: This comprehensive structural and functional characterization of a large cohort of patients with molecularly confirmed choroideremia indicates that certain parameters are not changing significantly with time while others are. The latter warrants a prospective natural history study, ultimately to be considered as outcome measures for interventional clinical trials.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CHOROIDAL NEOVASCULARIZATION IN FOUR INHERITED RETINAL DYSTROPHIES.

PURPOSE: To demonstrate the clinical utility of optical coherence tomography (OCT) angiography (OCT-A) in inherited retinal dystrophies complicated by choroidal neovascularization (CNV). METHODS: Optical coherence tomography angiography and structural OCT were performed using a 70-kHz spectral domain OCT system using the split-spectrum amplitude-decorrelation angiography algorithm. Semiautomated image processing software was used to segment and measure the CNV. RESULTS: Four participants were enrolled to study the following inherited retinal dystrophies complicated by CNV: choroideremia, EFEMP1-related retinopathy, Best vitelliform dystrophy, and adult-onset vitelliform dystrophy. Interpretation of fluorescein angiography was difficult because of abnormal retinal architecture but suggested the presence of CNV. Structural OCT revealed subretinal or subretinal pigment epithelium fibrovascular tissue, within which flow signal was observed on OCT-A. The CNV morphology varied from dense capillary networks in active lesions to asymptomatic large caliber loops. Baseline CNV vessel areas ranged from 0.07 mm to 0.98 mm. After treatment with intravitreal bevacizumab, the CNV in choroideremia decreased in the vessel area then rebounded, whereas the one in EFEMP1-related retinopathy remained largely unchanged. CONCLUSION: Optical coherence tomography angiography enables morphologic characterization and quantification of CNV in patients with retinal dystrophies despite distorted retinal architecture, can assess response to treatment, and may facilitate differentiation between active and regressed lesions.

Plateau iris in children.

Narrow iridocorneal angles, a very rare condition in the pediatric population, can lead to visual loss through angle closure glaucoma. In the workup for patients with narrow iridocorneal angles, plateau iris must be considered in the differential diagnosis. We describe 5 children with plateau iris, the youngest 5 years of age. All were confirmed using ultrasound biomicroscopy and were offered iridotomy for treatment.

Paraneoplastic syndromes in neuro-ophthalmology.

PURPOSE OF REVIEW: The aim of this review is to discuss and highlight the recent advances in our understanding of paraneoplastic syndromes in neuro-ophthalmology and their significance. RECENT FINDINGS: The pathophysiologic mechanism in neuro-ophthalmic paraneoplastic syndromes involves an immune response triggered by aberrant expression of onconeuronal antigens that cross-react with antigens in the visual system. Recently, 18-fluoro-deoxy-glucose/positron emission tomography with computed tomography scanning has emerged as a useful modality in diagnosing occult tumors responsible for paraneoplastic syndromes. Paraneoplastic optic neuropathy has been recently associated with the anti-CV2/CRMP-5 antibody. The use of serologic analysis of recombinantly expressed clones (SEREX) has led to the identification of new antigens associated with melanoma-associated retinopathy, such as visual arrestin, rhodopsin, titin, and mitofilin. Calcium-channel blockers and alemtuzumab have been found to improve visual function in cancer-associated retinopathy. Rituximab has been found to be effective in childhood opsoclonus-myoclonus syndrome. SUMMARY: A high index of suspicion is needed to diagnose neuro-ophthalmic paraneoplastic syndromes. There have been recent advances in our understanding of the pathophysiology and treatment of these disorders. This will facilitate early treatment of causative occult tumors and improves the prognosis.