Vitreous hyper-reflective dots and the macular thickness after cataract surgery.

PURPOSE: To assess the association between vitreous hyper-reflective dots (VHD) and the macular thickness changes following uneventful phacoemulsification. METHODS: In this prospective cohort study optical coherence tomography (OCT) examinations were performed preoperatively and 1 week, 1 month and 3 months postoperatively in patients undergoing cataract surgery. OCT images were analyzed for retinal central subfield thickness (CST) and preretinal VHDs. Surgeries were recorded for the assessment of lens fragments in the space of Berger. RESULTS: 111 eyes of 97 patient were enrolled of whom 69 (62.2%) were female. VHDs were seen in 25 eyes (22.5%) at week 1; in 21 eyes (18.9%) at month 1 and in 3 eyes (2.7%) at month 3. In all eyes with VHDs retro-capsular lens fragments were visible immediately after phacoemulsification. The number of VHDs significantly decreased over the postoperative period. There was a moderate correlation between the number of VHDs and CST at 1 month (r = 0.426, p<0.001). In eyes with VHD the CST averaged 238.8±17.6 µm (214-266) at 1 week; 276.1±63.5 µm (231-481) at 1 month and 285.1±122.3 µm (227-785) at 3 months. In eyes with no detectable VHDs CST averaged 235.9±23.3 µm (192-311) at 1 week; 240.1±21.6 µm (200-288) at 1 month and 242.2±21.3 µm (205-289) at 3 months. Although the differences among the assessment points were relatively low, there was a significant difference in general (p<0.001, Friedman test). CONCLUSION: In conclusion, VHDs seem to cause macular thickening throughout the postoperative course. The origin of VHDs is still unknown; however, they presumably represent lens fragments that provoke subclinical inflammation.

Modification of the Suprachoroidal Buckling Technique for the Treatment of Rhegmatogenous Retinal Detachment.

PURPOSE: To describe modification of the suprachoroidal buckling technique for the treatment of rhegmatogenous retinal detachment (RRD), which may improve the safety profile. METHODS: A single-surgeon foot-pedal-controlled automated suprachoroidal injection (SCI) of sodium hyaluronate 1%, namely ProVisc (Alcon Laboratories, Fort Worth, TX) was used for the treatment of RRD. MicroDose Injection Kit (MedOne Surgical, Sarasota, FL) including a connector and a 1-mL syringe, designed for subretinal injection, was used to adapt Constellation Vision System (Alcon Laboratories) console for SCI of ProVisc from the 1-mL syringe. RESULTS: This approach enables better surgeon control during SCI. Three highly myopic eyes of three patients with primary macula-on RRD and single superior peripheral retinal break were treated. Complete retinal reattachment was achieved in all eyes without complications. CONCLUSION: Injecting ProVisc under foot-pedal control provides a more precise and potentially safer suprachoroidal buckling technique compared with the manual technique with more variable injection speed and pressure.

Pathogenicity reclassification of the RPE65 c.1580A>G (p.His527Arg) - a case report.

BACKGROUND: It is of utmost importance to define the molecular diagnosis of patients with retinitis pigmentosa (RP) due to existing targeted therapeutic option: voretigene neparvovec.We provide clinical evidence for pathogenicity reclassification of variants of uncertain significance (VUSs) RPE65 c.1580A>G (p.His527Arg). MATERIALS AND METHODS: A case report of a 10-year-old boy with progressive vision loss. The patient manifested disease highly suggestive of RPE65 retinal dystrophy: nyctalopia, fairly good central vision, severely depressed full-field electroretinography responses and complete loss of peripheral fundus aut ofluorescence. RESULTS: Invitae Inherited Retinal Disorders Panel identified likely pathogenic mutation RPE65 c.499G>T (p.Asp167Tyr) and RPE65 c.1580A>G (p.His527Arg), variant of uncertain significance. Segregation analysis confirmed that these variants are in trans. CONCLUSIONS: We conclude that the variant RPE65 c.1580A>G (p.His527Arg) has contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as pathogenic. Therefore, patients with this specific variant in homozygous or compound heterozygous form would likely benefit from genetic treatment based on recombinant adeno-associated virus vector, providing a working RPE65 gene to act in place of a mutated RPE65 gene.

RPE65 c.353G>A, p.(Arg118Lys): A Novel Point Mutation Associated with Retinitis Pigmentosa and Macular Atrophy

Precise genetic diagnosis in RPE65-mediated retinitis pigmentosa (RP) is necessary to establish eligibility for genetic treatment with voretigene neparvovec: a recombinant adeno-associated viral vector providing a functional RPE65 gene. This case report aims to report a novel RP-related point mutation RPE65 c.353G>A, p.(Arg118Lys), a variant of uncertain significance associated with a severe clinical presentation and the striking phenotypic feature of complete macular atrophy. We report the case of a 40-year-old male with inherited retinal dystrophy, all features typical for the RPE65-associated RP, and marked macular atrophy. Genetic testing identified that the patient was a compound heterozygote in trans form with two heterozygous variants: RPE65 c.499G>T, p.(Asp167Tyr) and RPE65 c.353G>A, p.(Arg118Lys). Furthermore, short-wavelength and near-infrared autofluorescence patterns exhibited deficiencies specific to mutations in the visual cycle genes. To the best of our knowledge, RPE65 c.353G>A, p.(Arg118Lys) is the first described point mutation on this locus, among all other reported insertional mutations, currently classified as likely benign and of uncertain significance. We concluded that this variant contributed to the pathological phenotype, demonstrating its significance clearly to be reclassified as likely pathogenic. This being the case, patients with this specific variant in homozygous or compound heterozygous form would be likely candidates for genetic treatment with voretigene neparvovec.

RPE65 c.393T>A, p.(Asn131Lys): Novel Sequence Variant Detected.

Background: Leber congenital amaurosis (LCA) is a monogenic, but genetically heterogenous disease, and at least 27 genes are implicated. This case report is aimed at providing evidence to link the novel variant RPE65 c.393T>A, p.(Asn131Lys), variant of uncertain significance (VUS), to clinical phenotype and to set the ground for objective assignment of pathogenicity confidence. Case Presentation. A case report of a female patient with LCA who manifested with nystagmus, night blindness, profound visual deficiency, and peripheral involvement of the retina consistent with RPE65 dystrophy. A thorough clinical examination, diagnostic evaluation, and genetic testing were performed. The patient was a compound heterozygote in trans form: RPE65 c.304G>T, p.(Glu102∗) pathogenic, and RPE65 c.393T>A, p.(Asn131Lys), VUS. The latter variant is absent in healthy controls and is considered harmful on in silico prediction. Conclusions: We conclude that RPE65 c.393T>A, p.(Asn131Lys) contributed to the pathologic phenotype, demonstrating its significance clearly in the case presented, and should be reclassified according to the criteria of evidence as likely pathogenic. This being the case, patients with this specific variant are likely candidates for genetic treatment.

Analysis of association of risk factors for age-related macular degeneration.

PURPOSE: To evaluate the significance of risk factors and analyze their interrelationship in developing age-related macular degeneration (AMD). MATERIALS AND DESIGN: This is a multicenter, cross-sectional study conducted in eight ophthalmology centers in Europe. The STARS (Simplified Thea AMD Risk-Assessment Scale) questionnaire was used to assess 12 risk factors grouped in four major categories. We used Welch's t-test/F ratios to determine statistically significant changes. The principal component analysis was done to investigate the association between risk factors. RESULTS: There were 3297 participants included in our data analysis. Nineteen percent of patients had a high risk of developing AMD, whilst 45.92% and 34.85% had moderate and small risk, respectively. Atherosclerosis appeared as the most relevant risk indicator for AMD development (Cohen's d = 0.861). Tukey's post hoc analysis of the smoking variable showed that ex-smokers (p < 0.001) have a significantly high risk of developing AMD. The Welch's t-test showed pseudophakic patients have a higher risk of developing AMD than phakic ones. Then, we conducted the principal component analysis, which revealed a significant connection between smoking and male gender and between smoking and atherosclerosis. Pseudophakic patients were generally older and had more often myocardial infarction as compared to phakic patients. We showed that higher BMI, history of arterial hypertension, hypercholesterolemia, and atherosclerosis tend to occur together as risk factors for AMD. CONCLUSION: Risk factors evaluated in our study should be considered for the development of AMD.

Do Gender, Age, Body Mass and Height Influence Eye Biometrical Properties in Young Adults? A Pilot Study.

BACKGROUND: Do gender, age, body mass and height influence eye biometrical properties in young adults? METHODS: A total of 155 eyes (92 female, 63 male) of healthy subjects between the ages of 18 and 39 years were included in the study. The subjects' gender and age were recorded, and their body mass, height and biometrical properties of the eyes were measured. RESULTS: The male subjects had significantly thicker and flatter corneas and lower minimal rim-to-disk ratios than the female subjects did. In both genders, age showed strong, negative correlations with anterior chamber depth and pupil diameter and a positive correlation with lens thickness. We also found significant, negative correlations between body height and mass with keratometry measurements, negative correlations between body height and optic disk rim area and rim volume, and positive correlations between body mass and axial length in both genders. CONCLUSIONS: Biometric eye parameters differ among people. In addition to age and gender, which are usually taken into consideration when interpreting ocular biometry findings, we strongly suggest that body height and mass should be also routinely considered when interpreting eye biometry data, as these factors have an impact on ocular biometry.

COMBINED TREATMENT WITH BEVACIZUMAB AND TRIAMCINOLONE ACETONIDE FOR MACULAR EDEMA DUE TO RETINAL VEIN OCCLUSION.

The purpose of this study was to determine the efficacy of combined intravitreal bevacizumab and triamcinolone in the treatment of macular edema due to retinal vein occlusion. A prospective randomized trial was conducted in the Department of Ophthalmology, Osijek University Hospital Centre in Osijek including 51 patients divided into three groups depending on the drug received. The first group received 1.25 mg intravitreal bevacizumab, the second group received 1 mg intravitreal triamcinolone, and the third group received a combination of 1.25 mg bevacizumab and 1 mg intravitreal triamcinolone on the same day. Changes in the central macular thickness, intraocular pressure and visual acuity were monitored during the follow up period. The retinal perfusion status was evaluated by fluorescein angiography. The group that received combined treatment had better outcome in terms of reduction of macular thickness. There was no statistically significant intraocular pressure elevation among the three treatment groups or within each group of patients. A positive trend regarding visual improvement was observed in the group receiving combined treatment in spite of the lowest initial visual acuity, highest value of macular thickness and longest mean duration of symptoms. In conclusion, combined treatment with bevacizumab and triamcinolone for the treatment of retinal vein occlusion is more potent, safe, efficient and cost-effective. It can also be recommended because fewer injections are needed in patients undergoing treatment for macular edema.

SPECIFIC CHARACTERISTICS OF OCULAR BIOMETRIC FACTORS IN GLAUCOMATOUS PATIENTS WITH PSEUDOEXFOLIATIVE SYNDROME AS MEASURED BY OPTICAL LOW-COHERENCE REFLECTOMETRY.

The aim of the study was to assess biometric factor aberrations and differences among groups of eyes with cataract and pseudoexfoliative syndrome, cataract and pseudoexfoliative glaucoma, and cataract and primary open-angle glaucoma (POAG), and to determine biometric factors of the eye specific for the group of glaucomatous patients with pseudoexfoliative syndrome by use of optical low-coherence reflectometry. This retrospective study included 72 patients, and the study sample of 102 eyes was divided into the following three groups according to diagnosis: 29 eyes with pseudoexfoliative syndrome and cataract; 36 eyes with POAG and cataract; and 37 eyes with pseudoexfoliative glaucoma and cataract. Data on biometric measurements (central corneal thickness, pupillary diameter, anterior chamber depth, lens thickness, axial length, retinal thickness, astigmatism and white-to-white) obtained by use of optical low-coherence reflectometry on a Lenstar LS 900® (Haag-Streit International) were collected and analyzed by thorough survey of medical documentation of patients scheduled for cataract surgery at Department of Ophthalmology, Sveti Duh University Hospital in Zagreb, Croatia. Comparative analysis of the groups yielded statistically significant differences in central corneal thickness (F2/99=7.066; p=0.001) and lens thickness (F2/96=5.133; p=0.008). The group of eyes diagnosed with pseudoexfoliative glaucoma and cataract had a significantly thinner cornea as compared with the other two groups and a significantly thicker lens as compared with the group of eyes with POAG and cataract. In conclusion, optical low-coherence reflectometry revealed differences in biometric factors among the three groups of eyes, with a statistically significantly thinner cornea and thicker lens in the group of glaucomatous patients with pseudoexfoliative syndrome.

Dermis-Fat Graft for Correction of Recurrent Severe Upper Eyelid Retraction in Graves' Orbitopathy.

Dermis-fat graft has been proven as a useful replacement tissue for eyelid and orbit reconstruction, but there is no evidence in the literature that it can be used for correction of upper eyelid retraction. This is the first report that presents two cases (four eyelids) of dermis-fat graft usage as a spacer in the treatment of severe recurrent upper eyelid retraction due to Graves' orbitopathy. Improvement was achieved with minimum complications, patient symptoms were reduced, and the results were stable almost three years after the procedure.

Single-Stage Orbital Socket Reconstruction Using the Oversized Dermis Fat Graft and the 22 mm Silicone Orbital Implant after an Extended Enucleation.

We would like to present a surgical technique of orbital socket reconstruction using oversized dermis fat graft and 22 mm silicone orbital implant in a single-stage after extended enucleation in two patients with massive local recurrence of anteriorly located choroidal melanoma previously treated with endoresection. Orbital tissues en bloc were removed leaving conjunctival lining only at the fornices. Simultaneously, the 22 mm silicone sphere was implanted deeply into the orbit and covered with the oversized dermis fat graft of 30 mm in height and 35 mm in length with 20 mm of the fat thickness. The graft was sutured to the residual forniceal conjunctiva with interrupted 6/0 absorbable sutures overlapping conjunctiva with the graft edge for 2 mm to facilitate the epithelization. Epithelization was completed in two months, leaving well-formed fornices with good fitting of the prosthesis. The key point of orbital socket reconstruction after extended enucleation is to restore conjunctival lining prior to volume. Thus, whenever facing a massive volume and conjunctival lining loss, simultaneous insertion of the 22 mm silicone sphere deep into the orbit combined with oversized dermis fat graft is, in our opinion, the method of choice. It proved to be safe and effective with favourable long-term results.

Ultrasound reliability in detection of retinal tear in acute symptomatic posterior vitreous detachment with vitreous hemorrhage.

Cross-sectional study of 75 consecutive patients presenting with acute symptomatic posterior vitreous detachment (ASPVD) and vitreous hemorrhage was conducted at University Eye Clinic, University Hospital "Sveti Duh", Zagreb, Croatia. To check ultrasound reliability in detecting retinal tears in patients with ASPVD, transpalpebral ultrasound of the eye and the orbit was performed followed by fundus examination initially and in 6wk period. In 13 (17%) patients membranous lesion with ultrasound characteristics of retinal tear was detected. Ophthalmoscopy confirmed the diagnosis in 8/13 patients. In 62/75 patients neither ultrasound nor clinical examination revealed retinal tear. Sensitivity of ultrasound examination was 100%, specificity 92%, positive predictive value 62% and negative predictive value 100%. Ultrasound proved to be a reliable and accurate method for detection of retinal tears in ASPVD. Given the high sensitivity and negative predictive value, negative result on B-scan ultrasound excludes the probability of the retinal tear with a high degree of certainty.

Histopathological changes in involutional lower eyelid entropion: the tarsus is thickened!

OBJECTIVE: Evaluation of histopathological changes in lower eyelid involutional entropion. DESIGN: Case-control, comparative study at a single institution. PARTICIPANTS: A total of 20 consecutive patients with previously untreated involutional lower eyelid entropion and 20 matching patients with lateral lower eyelid basal cell carcinoma (BCC). METHODS: Patients with involutional entropion were operated using our modified surgical method, and patients with BCC underwent full-thickness pentagonal excision with 3-mm surgical margins. Histopathological analysis of the full-thickness eyelid specimens of both groups included measurements of tarsal thickness and height, thickness of the pretarsal orbicularis oculi muscle, diameter of muscle fibres, and qualitative changes in lower eyelid retractor attachment. RESULTS: The tarsus was significantly thicker in the entropion group (p = 0.006). The mean tarsal thickness was 1.40 ± 0.32 mm, whereas in the BCC group it was 1.16 ± 0.19 mm. There was no statistically significant difference in the tarsal height and the thickness of the pretarsal orbicularis oculi muscle between the 2 groups. In the entropion group, 60% of the lids had total and 35% partial dehiscence of the retractor, whereas in the BCC group, dehiscence was found in only 45% of the lids. The difference was statistically significant (p = 0.002). CONCLUSIONS: To the best of our knowledge, this is the first histopathological study documenting thickening of the tarsus in involutional lower eyelid entropion. Moreover, dehiscence of the lower eyelid retractor was proven histopathologically in 95% of the entropic lids. With this in mind, correction of vertical instability should be mandatory in involutional lower eyelid entropion repair.

Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia.

AIM: To present and evaluate a new screening protocol for amblyopia in preschool children. METHODS: Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic. RESULTS: 78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively. CONCLUSION: The ZAPS study used the most discriminative VA test with optotypes in line as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia.

Intravitreal Bevacizumab and Cardiovascular Risk in Patients with Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies.

INTRODUCTION: Intravitreal bevacizumab (IVTB) is used to treat age-related macular degeneration (ARMD), although its use is off-label and its cardiovascular safety has not been unequivocally established. OBJECTIVES: Our objective was to assess the cardiovascular safety of IVTB in patients with ARMD. METHODS: We conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs) and observational studies. RESULTS: Of the 2028 non-duplicate records, five RCTs versus ranibizumab (N = 3038, 12/24 months), four RCTs comparing different regimens (N = 809, 12/23 months), one RCT versus pegaptanib, photodynamic therapy (PDT), or sham (N = 131, 12 months), and three observational studies versus PDT, ranibizumab, or pegaptanib (~150,000 or 1666 patients/12 months and 317 patients/1-2 years, respectively) had a low risk of bias/high quality and ≥20 patients per arm with ≥6 months and ≥3 injections of treatment. RCT-based comparisons with PDT or pegaptanib are negligible. Observational data have not demonstrated differences [all-cause mortality, myocardial infarction (MI), stroke], but the level of evidence is "very low" (imprecise, indirect). RCT-based comparisons with ranibizumab did not demonstrate differences regarding some outcomes, although certain point estimates were at the level of a relevant harm/benefit [all-cause mortality odds ratio (OR) 1.103, 95 % confidence interval (CI) 0.641-1.898; vascular mortality OR 1.380, 95 % CI 0.476-3.997; MI OR 0.551, 95 % CI 0.265-1.146; stroke OR 0.657, 95 % CI 0.260-1.660; transitory ischemic attack OR 1.536, 95 % CI 0.444-5.313; atherothrombotic events (ATEs) OR 1.007, 95 % CI 0.641-1.593; venous thromboembolism OR 2.325, 95 % CI 0.963-5.612] or suggested a higher risk with bevacizumab (hypertension OR 7.512, 95 % CI 1.056-52.3), but estimates were based on sparse data, were extremely imprecise, and commonly exhibited considerable heterogeneity/inconsistency. The level of evidence per outcome was "low" or "very low". Observational data did not demonstrate difference (all-cause mortality, MI, stroke), or suggested a higher risk with bevacizumab (ATE), but were imprecise and indirect (level of evidence "very low"). RCT-based comparisons of different IVTB regimens suffered from the same limitations. CONCLUSION: Published data on IVTB in AMRD provide only a low level of evidence on its cardiovascular safety and do not support any finite conclusions.