Peripheral and central retinal vascular changes in asymptomatic family members of patients with familial exudative vitreoretinopathy.

PURPOSE: To evaluate the peripheral vascular changes and effects of these on macular microvasculature in asymptomatic family members of familial exudative vitreoretinopathy (FEVR) patients. METHODS: This is a retrospective study including 61 eyes of asymptomatic family members of FEVR patients. Retinal abnormalities were assessed via ultra-widefield fluorescein angiography (UWF-FA) and optical coherence tomography angiography (OCTA). The eyes were grouped into 3: the first group comprised of eyes with normal findings on UWF-FA; the second group comprised of eyes with abnormal findings on UWF-FA but without any retinal ischemia; and the third group involved eyes with retinal ischemia or neovascularization. RESULTS: Best corrected visual acuity (BCVA) was 20/20 in all eyes. Forty eyes (65.6%) had abnormalities on UWF-FA. The most common feature was peripheral vascular looping, increased tortuosity, and anastomosis (63.9%). ODM/ODD ratio was higher in group 3 compared to groups 1 and 2. Deep foveal VD was lower in group 1 compared to groups 2 and 3. The mean FAZ area and perimeter were smaller in groups 2 and 3 compared to group 1. CONCLUSION: Even asymptomatic family members of FEVR patients may have significant peripheral retinal vascular abnormalities which may be associated with smaller optic disc, macular ectopia, and macular microvascular changes.

Severe anterior persistent fetal vasculature: the role of anterior retinal elongation on prognosis.

PURPOSE: This study aims to investigate surgical outcomes of eyes with severe anterior persistent fetal vasculature (PFV) and the role of associated anatomical anomalies on prognosis. METHODS: This is a retrospective, comparative case series of 32 eyes of 31 patients who underwent vitreoretinal surgery for severe anterior PFV, defined as fibrovascular tissue totally covering the back of cataractous lens. Based on the degree of anterior retinal elongations, cases were classified as follows: group 1, eyes with well-developed pars plana and minor/no abnormalities (n = 11, 34%); group 2, eyes with partially developed pars plana and broad-based elongations (n = 9, 28%); and group 3, eyes with no visible pars plana and fibrovascular membrane having 360° continuity with peripheral retina (n = 12, 38%). Complications and functional and anatomical outcomes were investigated. RESULTS: The median surgical age was 2 (1-12) months. The median follow-up was 26 (6-120) months. Seventy-three percent in group 1 achieved finger counting or better vision with a single surgery and without any pupillary/retinal complication. Groups 2 and 3 required 2.1 ± 0.9 and 2.6 ± 1.2 surgeries on average. Pupillary obliteration and RD occurred in 33% and 22% in group 2 and 58% and 67% in group 3. Retina remained attached after silicone oil removal in 89% of group 2 and 25% of group 3. Phthisis developed in 50% in group 3. CONCLUSION: Peripheral retinal anomalies are common in severe anterior PFV and have a major impact on prognosis. Prognosis is favorable in cases with mild-to-moderate anomalies with appropriate management of possible retinal tears. In eyes with 360° retinal elongations, severe fibrous proliferation and eventual eye loss are common.

LONG-TERM EFFECTS OF ANTI-VEGF MONOTHERAPY FOR RETINOPATHY OF PREMATURITY ON THE RETINAL AND REFRACTIVE DEVELOPMENT OF EYE.

PURPOSE: To evaluate vascular maturation of retina, axial, refractive, and foveal development after anti-VEGF treatment including bevacizumab, ranibizumab, and aflibercept in infants with treatment requiring retinopathy of prematurity (ROP) in long term. METHODS: This retrospective chart review study included children with a history of any anti-VEGF monotherapy for ROP in Zone 1 or posterior Zone 2 who have reached at least 24 months of corrected age. The records of ophthalmologic examination including strabismus evaluation, visual acuity measurement, refractive and axial measurements, optical coherence tomography, and fundus fluorescein angiography examinations with RetCam III were reviewed. RESULTS: A total of 36 eyes of 18 children met the inclusion criteria. The mean gestational age at birth was 27.8 2.13 (23-30) weeks, and ocular assessments were performed between 33 and 61.5 (mean: 42.58 8.6) months of corrected age. Treatment was with bevacizumab in 10 eyes, with ranibizumab in 14 eyes, and with aflibercept in 12 eyes. The mean spherical equivalent was -0.25 1.82; axial length was 20.81 0.62 mm. There was no significant difference among three anti-VEGF groups regarding the abnormal vascular retinal development ( P = 0.183) or leakage ( P = 0.842) on fluorescein angiography. CONCLUSION: All the anti-VEGF agents provided similar adequate axial and refractive development as well as similar abnormal vascular development in the peripheral retina. The long-term impact of this abnormally vascularized peripheral retina is a curiosity issue. From this point of view, it is an important need to determine the follow-up period and method after the anti-VEGF treatment for ROP.

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Comparison of the effects of operating microscopes with light emitting diode and halogen light source on the eye: a rabbit study.

PURPOSE: To evaluate the potential toxicity of operation microscopes with halogen and light emitting diode (LED) light source on the rabbit eyes. MATERIALS AND METHODS: Thirty-two eyes of 16 male New Zealand pigmented rabbits were involved in the study. The rabbits were divided into two groups according to the type of light source applied. Only one eye of each rabbit was exposed to illumination light, unexposed fellow eyes served as the control group. Experimental groups included group 1 exposed to halogen light for 2 h and evaluated 1 day and 1 week after the illumination, group 2 exposed to LED light for two hours and evaluated 1 day and 1 week after the illumination. On the first and seventh days after exposing the light, we evaluated the rabbit corneas using in vivo confocal microscopy (IVCM). At the end of the seventh day, the Hematoxylin-eosin staining and TUNEL staining were performed to investigate the presence of apoptosis in the retina and retina pigment epithelium. RESULTS: Early IVCM findings revealed corneal epithelial cell ovalization and indistinct intercellular borders in the halogen light group. We also observed more increase in the keratocyte density index (23.7% vs 14.1%, p = 0.001, respectively) and the Bowman reflectivity index (12.4% vs 4.1%, p = 0.001, respectively) at first day of the light exposure in halogen light group compared to LED light group. However, late IVCM indicated that these findings disappeared one week later. No apoptosis was observed in the corneal and retinal layers in early and late examination groups. CONCLUSION: The present experimental study demonstrated that both halogen and LED lights, which were commonly used for microscopic eye surgery, had no sustained adverse effect on the cornea and retina of the rabbits; however, halogen light had a temporary adverse effect on corneal epithelium and stroma, which resolved within 1 week.

Optic nerve ultrasonography in monitoring treatment efficacy in pediatric idiopathic intracranial hypertension.

PURPOSE: Measurement of optic nerve sheath diameter (ONSD) with ocular ultrasonography (USG) is a noninvasive technique that can be readily used to determine clues of increased intracranial pressure. In this study, we aimed to determine the role of optic nerve sheath diameter measurements in the diagnosis and follow-up of pediatric patients with idiopathic intracranial hypertension (IIH). METHODS: Eight patients with a diagnosis of IIH with a median age of 11.7 (range 4.5-17) years were examined prospectively. During follow-up, orbital ultrasonography (USG) was performed immediately prior to lumbar puncture (LP) and at 24 h, at 1 week, and between 1 and 18 months after LP. Cranial MRI examinations and automated visual field assessments were performed at baseline and at 3 months, and both measurements were compared with each other. RESULTS: The mean cerebrospinal fluid opening pressure (37.75 ± 12.64 cm H2O) and the mean ONSD (5.94 ± 0.46 mm) were correlated. The median follow-up was 16 (range, 12-18 months), and ONSD regressed gradually consistent with clinical and radiologic improvement during follow-up. CONCLUSIONS: To the best of our knowledge, this is the first prospective pilot study performed on pediatric patients with IIH using orbital USG for ONSD measurements. Despite the small sample size, the present study indicated that orbital USG may be used as a promising noninvasive tool to diagnose increased intracranial pressure and for monitoring treatment efficacy in this special patient population.

Real-life comparison of the viewing angle and the image quality of two commonly used viewing systems for vitreoretinal surgery

Background/aim: To compare the clinical use, image quality and viewing angle of a commonly used contact wide angle viewing (WAV) system (Advanced Visual Instruments (AVI) Panoramic Imaging Systems, NY, USA) with a commonly used noncontact WAV system (Leica RUV800, Leica Microsystems, Switzerland). Materials and methods: Images of 42 consecutively operated eyes were obtained with both systems at the same surgical stages and were compared for image quality using the Imatest Master 4.5.13 (Imatest LLC, Boulder, USA) software. The viewing angles of the images were calculated using the optic disc sizes measured from the OCT and infrared fundus images. The 68-degree AVI lens was compared with the 90-dioptre (D) Leica RUV800 lens, while the 130-degree AVI lens was compared with the 132-D Leica RUV800 lens. The surgical assistants were asked to grade the difficulty of holding the lens in place from 1 to 10, 1 being the easiest and 10 being the most difficult. Results: The contact system provided wider viewing angles with higher quality compared to the noncontact system both under fluid and air media. The difference was clinically significant in eyes with impaired corneal clarity, very high myopia, or small pupil. The difficulty of holding the lens in place ranged from 4 to 7, and decreased gradually with practice. Conclusions: Both WAV systems provided high image quality and adequate viewing angles in most cases. However, the contact system appeared to provide a superior image quality and/or a wider viewing angle in more challenging situations. The difficulty of holding the contact lens in place was found to be moderate.

Bi-allelic Mutations in KLHL7 Cause a Crisponi/CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa.

Crisponi syndrome (CS)/cold-induced sweating syndrome type 1 (CISS1) is a very rare autosomal-recessive disorder characterized by a complex phenotype with high neonatal lethality, associated with the following main clinical features: hyperthermia and feeding difficulties in the neonatal period, scoliosis, and paradoxical sweating induced by cold since early childhood. CS/CISS1 can be caused by mutations in cytokine receptor-like factor 1 (CRLF1). However, the physiopathological role of CRLF1 is still poorly understood. A subset of CS/CISS1 cases remain yet genetically unexplained after CRLF1 sequencing. In five of them, exome sequencing and targeted Sanger sequencing identified four homozygous disease-causing mutations in kelch-like family member 7 (KLHL7), affecting the Kelch domains of the protein. KLHL7 encodes a BTB-Kelch-related protein involved in the ubiquitination of target proteins for proteasome-mediated degradation. Mono-allelic substitutions in other domains of KLHL7 have been reported in three families affected by a late-onset form of autosomal-dominant retinitis pigmentosa. Retinitis pigmentosa was also present in two surviving children reported here carrying bi-allelic KLHL7 mutations. KLHL7 mutations are thus associated with a more severe phenotype in recessive than in dominant cases. Although these data further support the pathogenic role of KLHL7 mutations in a CS/CISS1-like phenotype, they do not explain all their clinical manifestations and highlight the high phenotypic heterogeneity associated with mutations in KLHL7.

Elevated serum ferritin level with cataract of spectacular morphology: Hyperferritinemia-cataract syndrome.

Hyperferritinemia-cataract syndrome, characterized by high serum ferritin concentration and cataracts in early life, remains a less-known rare disease, with fewer than 100 families reported worldwide. Though benign, high ferritin levels frequently result in misdiagnosis with iron storage disease, and patients can be exposed to unnecessary, even invasive, evaluation and treatment procedures. The presence of cataract together with isolated serum ferritin elevation should alert clinicians to consider this syndrome. We herein present a new family with hyperferritinemia-cataract syndrome to increase clinical awareness.

Prediction of Descemet Membrane Perforation During Deep Anterior Lamellar Keratoplasty in Patients With Keratoconus With Stromal Scar.

OBJECTIVES: To report big-bubble deep anterior lamellar keratoplasty (DALK) in patients with keratoconus with corneal stromal scar, and to investigate factors that can influence intraoperative Descemet membrane (DM) perforation. METHODS: A retrospective study included patients with keratoconus with central stromal scar that underwent DALK using the big-bubble technique. Best spectacle-corrected visual acuity (BSCVA), keratometry, minimum corneal thickness (MCT), stromal scar depth, and endothelial cell density (ECD) were recorded. Receiver operating characteristic (ROC) curves were analyzed to predict an intraoperative perforation related to stromal scar. RESULTS: Thirty-eight eyes of 38 patients with keratoconus (mean age: 30.0±9.2 years) were included in this study. Thirty-four eyes had successful DALK; in four eyes, the procedure was converted to penetrating keratoplasty because of DM macroperforations. Successful big-bubble formation was achieved in 24 of 38 (63.2%) eyes, whereas in 10 eyes, manual dissection was used to complete the DALK. Mean preoperative and postoperative second year BSCVA were 1.3 (±0.4) and 0.5 (±0.2) logarithm of the minimum angle of resolution (P<0.001), keratometry values were 65.5±7.4 and 42.8±7.8 diopters (P<0.001), and ECD were 2,740±359 and 2,279±452 cells/mm (P<0.001), respectively. Using ROC analysis, the area under curve value to predict DM perforation was found to be 0.792 (scar/MCT ratio, P=0.04) and the best cutoff point for scar depth/MCT ratio was 53%. CONCLUSION: Big-bubble DALK is effective in patients with keratoconus with stromal scars. Scar depth/MCT ratio seems to predict the DM perforation.

Strabismus in Retinopathy of Prematurity: Risk Factors and the Effect of Macular Ectopia.

Objectives: This study aimed to examine factors associated with strabismus in patients with retinopathy of prematurity (ROP) and the relationship between strabismus and macular ectopia. Materials and Methods: Patients with ROP were divided into three groups: Group 1, patients with spontaneous regression (n=45); Group 2, patients who received laser treatment (n=70); and Group 3, patients who underwent surgical treatment (n=91). Rates of anisometropia, amblyopia, nystagmus, macular ectopia, and retinal pathologies were evaluated and their impacts on strabismus development were determined. Disc-to-fovea distance (DFD) was measured from color fundus photographs and the correlation of macular ectopia with severity of strabismus was evaluated. Results: A total of 206 patients were included. Rates of anisometropia, amblyopia, nystagmus, macular ectopia, retinal pathologies causing vision loss, and strabismus were higher in Group 3 (p=0.0001) and correlated with higher stages of ROP (p=0.0001). Macular ectopia (p=0.005), retinal pathologies (p=0.005), and amblyopia (p=0.012) had the strongest impact on strabismus development in ROP patients. DFD and strabismus severity were not significantly correlated (p=0.364). Mean visual acuity (VA) was significantly higher in orthophoric patients compared to those with esotropia and exotropia (p=0.027). Esotropic patients had lower VA compared to patients with exotropia, but this finding was not statistically significant (p=0.729). Conclusion: Presence of macular ectopia, retinal pathologies, and amblyopia were the most strongly correlated risk factors for strabismus development in ROP patients. DFD was not associated with severity of strabismus. Exotropia was mostly related to higher DFD and a possible relationship between esotropia and lower VA was observed.

Surgical outcomes of posterior persistent fetal vasculature syndrome: cases with tent-shaped and closed funnel-shaped retinal detachment.

BACKGROUND/OBJECTIVES: To determine the role of vitreoretinal surgery (VRS) for two different forms of posterior persistent fetal vasculature syndrome (PFVS); with tent-shaped tractional retinal detachment (TRD) and closed funnel-shaped TRD. SUBJECTS/METHODS: Retrospective, single surgeon, consecutive case series of 52 eyes of 44 patients with posterior PFVS who underwent VRS. Cases were divided into "tent-shaped TRD" and "funnel-shaped TRD" groups based on the preoperative TRD configuration. Associated anomalies, functional and anatomical outcomes were evaluated. The cosmetic appearance was defined as poor if there was phthisis bulbi, gross buphthalmos, or corneal opacification; acceptable if there was apparent leukocoria; and excellent if none were noted at the last follow-up. RESULTS: Thirty eyes of 29 patients presented with tent-shaped TRD; 70% of which obtained counting fingers or better vision and 90% showed significant reversal of tenting achieving retinal reattachment. The cosmetic appearance was excellent in 87%. Two eyes (7%) became phthisic. Twenty-two eyes of 15 patients presented with funnel-shaped TRD and leukocoria; 45% achieved LP vision and 70% of patients with bilateral pathology had LP in at least one eye. The cosmetic appearance was acceptable to excellent in 73%. Three eyes (14%) became phthisic, one (5%) of which required enucleation. The median follow-up time was 16 (6-71) months. CONCLUSIONS: VRS often provides functional vision and anatomy in posterior PFVS with tent-shaped TRD morphology. In the funnel-shaped TRD morphology, where no treatment has historically been recommended, surgery may be considered with an aim of restoring light perception and globe preservation, particularly in bilateral cases.

Clinical and genetic characteristics of retinoblastoma patients in a single center with four novel RB1 variants.

AIM: To assess the clinical and genetic characteristics of children diagnosed with retinoblastoma (RB) at Gazi University Faculty of Medicine's Department of Pediatric Oncology. METHODS: All cases diagnosed with RB and received treatment and follow-up in the Ophthalmology and Pediatric Oncology Department, October 2016 to May 2021 were evaluated retrospectively. The RB1 gene was analyzed by next-generation sequencing (NGS) technique in DNAs obtained from peripheral blood samples of the patients. RESULTS: This study included 53 cases with 67 RB-affected eyes during the study period. The mean age was 24.6 (median: 18.5, range: 3-151)mo. There were 15 (22.3%) Group D eyes and 39 (58.2%) Group E eyes. The RB1 gene was sequenced by the NGS method in 19 patients. Heterozygous RB1:NM_000321.3: c.54_76del (p.Glu19AlafsTer4) variant was detected in a 15-month-old female with bilateral RB. Heterozygous RB1:NM_000321.3: c.1814+3A>T variant was detected in a 5.5-month-old male with bilateral RB. The intronic RB1:NM_000321.3: c.1332+4A>G variant was detected in patient 14, a 13-month-old male with unilateral RB. The RB1:NM_000321.3: c.575_576del (p.Lys192SerfsTer10) variant was found in an 18-month-old female with an allele frequency of 37%. These variants have not been reported in the literature and mutation databases. CONCLUSION: Four novel variants are described and one of them is found in two different patients. This data is crucial for assessing prognosis. It serves as a guide for estimating the long-term risk of secondary malignancy as well as the short-term risk of developing additional malignancies in the same eye and the other eye.

Cyclopentolate eye drops-induced anaphylaxis in an infant.

BACKGROUND: Cyclopentolate is frequently used as a mydriatic agent during ophthalmological examinations in childhood and hypersensitivity reactions associated with this drug are rare. We aim to report an infant who experienced anaphylaxis due to cyclopentolate eye drops. CASE: A nine-month-old girl, who was being followed up with a diagnosis of retinoblastoma, presented for consultation for urticaria, cough, stridor, and dyspnea that developed after the administration of topical cyclopentolate to the eyes. The patient was diagnosed with anaphylaxis and treated with adrenaline. During the follow-up, tropicamide was used safely as an alternative drug. CONCLUSIONS: In children, hypersensitivity reactions due to cyclopentolate are very rare. Only four pediatric patients were reported in the literature to have developed an allergic reaction after the administration of cyclopentolate eye drops. We present here the youngest patient who developed anaphylaxis with cyclopentolate eye drops. Anaphylaxis due to cyclopentolate should be kept in mind, rapidly recognized, and treated when a reaction develops.

Pseudo-hyaloidal Stalk in Anterior Persistent Fetal Vasculature: A Report of Two Cases.

Persistent fetal vasculature (PFV) syndrome is characterized by abnormal regression of the fetal hyaloid system and may occur in various forms. In this report, two atypical cases associated with posterior capsular defect and ectopic lens material located along Cloquet's canal are discussed. Ultrasonography of these patients presenting with bilateral total cataracts revealed a hyaloidal stalk extending from the optic nerve head to the retrolental area. During lensectomy, it was observed that lens particles were moving anteriorly from the central mid-vitreous to the aspiration port and that the posterior capsule was developmentally defective. There was no pathological vascular remnant, rather the lens material partially filled Cloquet's canal through the opening in the posterior capsule and created a pseudo-stalk appearance on the preoperative ultrasonography. We aim to discuss possible mechanisms underlying these cases, which may help to improve our understanding of the PFV spectrum.

External Drainage Alone Versus External Drainage With Vitrectomy in Advanced Coats Disease.

PURPOSE: To evaluate the efficacy of transscleral drainage of subretinal fluid (TDSRF) with and without pars plana vitrectomy (PPV), which are performed as an adjunct to ablative therapies in advanced Coats disease. DESIGN: Retrospective, comparative case series. PATIENT POPULATION: A total of 31 eyes from 31 consecutive patients with advanced Coats disease at an average age of 47.8 ± 34.2 (2-156) months at the time of the surgery, who underwent TDSRF alone or in combination with PPV. METHODS: Main outcome measurements were LogMAR visual acuity values, anterior and posterior segment findings, need for further surgery, laser photocoagulation, and anti-vascular endothelial growth factor (anti-VEGF) treatment. Anatomical success was defined as the maintenance of retinal reattachment without any further surgery during follow-up. RESULTS: Sixteen patients underwent TDSRF alone, and 15 patients underwent combined TDSRF and PPV. Mean follow-up time was 34.8 ± 32.9 months (6-128). Anatomical success rate of combined TDSRF and PPV was higher than that of TDSRF alone (93.8% vs 75%, respectively). The incidence of epiretinal membrane formation, number of laser photocoagulation procedures, and anti-VEGF treatments were statistically significantly higher in the group that underwent TDSRF alone than in those who had combined TDSRF and PPV in the long term. There was an improvement in vision in only 4 eyes (12.9%) (all >3 years old at presentation) during the follow-up. CONCLUSIONS: Combined TDSRF and PPV appears to be more effective in controlling the disease than TDSRF alone, as an adjunct to ablative procedures for the treatment of advanced Coats disease. The need for additional treatment is much less with the addition of PPV.