Prediction of long-term visual outcome of idiopathic full-thickness macular hole surgery using optical coherence tomography parameters that estimate potential preoperative photoreceptor damage.

PURPOSE: To identify optical coherence tomography (OCT) parameters that predict postoperative best corrected visual acuity (BCVA) and are based on recent understanding of the pathomechanism of idiopathic full thickness macular hole (iFTMH) formation and closure. METHODS: A retrospective consecutive case series of patients who had macular hole (MH) surgery at our institution between 2016 and 2022 was performed. 32 eyes of 30 patients were selected with at least 12 months of follow-up, closed MH and good quality OCT at each visit. Univariate correlation analysis, multiple logistic regression with forward stepwise selection, and Akaike's Information Criterion (AIC) were used to identify the best predictors for postoperative BCVA at 6 and 12 months (M), and final (≥ 12 M) visits, and a new OCT index was created. Abilities of best models/indices to predict < 0.30 logMAR (> 20/40) BCVA were compared to macular hole index (MHI) using the area under the receiver operating curve (AU-ROC) analysis. RESULTS: Statistical analysis revealed base diameter (B) (6 M), preoperative BCVA and B (12 M) and smaller ELM-GCL distance (A), and B (final visit) as predictors for postoperative BCVA. AU-ROC analysis indicated greatest AUC at 6 M for MHI and B (0.797, p = 0.004 and 0.836 p = 0.001, respectively) and for the new A/B index at 12 M and final visit (0.844, p = 0.002 and 0.913, p = 0.003, respectively). CONCLUSION: Our study suggests that MHI and B can be useful predictors of short term BCVA while the new A/B index that incorporates OCT parameters indicating potential preoperative photoreceptor damage may be a good predictor for long term postoperative BCVA. Our findings support the theory that initial hole formation mechanisms and photoreceptor damage define visual prognosis.

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

Analysis of the Association between Retinal Artery Occlusion and Acute Ischaemic Stroke/ST-Elevation Myocardial Infarction and Risk Factors in Hungarian Patients.

Background and Objectives: We aimed to analyse data on retinal artery occlusion (RAO) patients to explore correlations with acute ischaemic stroke (AIS), ST-elevation myocardial infarction (STEMI), and cardio/cerebrovascular comorbidities. Patients and Methods: Our retrospective cohort study included 169 RAO and 169 age- and gender-matched control patients. We examined the association of AIS, STEMI, and related comorbidities such as hypertension (HT), type 1 and type 2 diabetes (T1DM and T2DM, respectively), hyperlipidaemia, and ischaemic heart disease (IHD) with RAO. We also recorded atrial fibrillation in our RAO patients. Results: Our results demonstrated that RAO patients developed both AIS and STEMI at a significantly higher rate compared to controls (p < 0.001 for both). We also found that RAO patients had a significantly higher prevalence of HT and hyperlipidaemia (p1 = 0.005, p2 < 0.001) compared to controls. Multiple risk factors together significantly increased the odds of developing AIS and STEMI. Conclusions: Our results suggest that through identifying and treating the risk factors for RAO patients, we can reduce the risk of AIS, STEMI, and RAO of the fellow eye. Considering that ophthalmologists are often the first detectors of these cardiovascularly burdened patients, collaboration with colleagues from internal medicine, cardiology, and neurology is essential to achieve secondary prevention.

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes.

BACKGROUND/AIMS: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'. INTERVENTION: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks. RESULTS: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. Objective: To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. Design, Setting, and Participants: This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. Interventions: Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. Main Outcomes and Measures: Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 µm to 36 µm for CST. Results: Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) µm in the SB11 group vs -100 (5) µm in the ranibizumab group, with an adjusted treatment difference of -8 µm (95% CI, -19 to 3 µm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. Conclusions and Relevance: These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.

Analysis of intravitreal bevacizumab treatment for macular oedema due to retinal vein occlusion.

PURPOSE: Our aim was to analyse the clinical effect of intravitreal bevacizumab treatment for macular oedema due to central/branch retinal vein occlusion (CRVO/BRVO). The end points were final best-corrected visual acuity (BCVA), BCVA improvement, final central 1-mm macular subfield thickness (CST) and change in CST. METHODS: Our study included 34 CRVO and 25 BRVO patients. Patients received intravitreal bevacizumab (IVB) treatment at our department. Our control group consisted of 50 CRVO and 30 BRVO patients, who had not received this treatment because their disease developed before the anti-VEGF treatment became available. For statistical analysis, two-sample t-test, Pearson's correlation, and ANOVA were used. The level of significance was defined at p < 0.05. RESULTS: With the two-sample t-test we found significant improvement of BCVA in the IVB-treated group (CRVO: 0.171 ± 0.270, p1 = 3.25×10-4; BRVO: 0.215 ± 0.282, p2 = 5.52×10-4). The difference in BCVA improvement was also significant compared to the control group (CRVO: p1 = 3.46×10-4; BRVO: p2 = 0.003). Significant decrease was observed in the CST in the treated group (CRVO: -345.114 ± 280.577, p1 = 6.94×10-9; BRVO: -151.875 ± 174.341, p2 = 1.67×10-4). In case of BRVO patients the final BCVA was significantly better in the treated group (0.617 ± 0.334) compared to the control group (0.406 ± 0.357), p = 0.016. CONCLUSION: IVB treatment results in significantly better final visual acuity and leads to significantly increased BCVA improvement compared to patients with RVO-induced macular oedema receiving no treatment.

Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X.

Purpose: Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). Methods: A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Results: Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Conclusion: Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.

Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene.

PURPOSE: NEUROD1 is a tissue-specific basic helix loop helix (bHLH) protein involved in the development and maintenance of the endocrine pancreas and neuronal elements. Loss of NEUROD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. Heterozygous loss-of-function mutations in NEUROD1 have previously been described as a cause of maturity-onset diabetes of the young (MODY) and late-onset diabetes. To date, homozygous loss-of-function NEUROD1 mutations have only been detected in two patients. Both mutations caused permanent neonatal diabetes and severe neurologic defects, including visual impairment. However, a detailed ophthalmological phenotype of this novel syndrome has not yet been reported. Our aim was to characterize the ophthalmological phenotype associated with the previously reported homozygous c.427_428CT mutation in the NEUROD1 gene. METHODS: The female patient was investigated on multiple occasions between 2009 (age 14) and 2014 (age 19), including visual acuity testing, automated perimetry, funduscopy, anterior-segment imaging, optical coherence tomography of the posterior pole, standard full-field electroretinography, and fundus-autofluorescence imaging. RESULTS: The patient had nyctalopia, blurry vision, and visual field constriction from early childhood. Her best corrected visual acuity ranged between 20/25 and 15/25 during the investigation period. Perimetry showed concentric constriction of the visual field, sparing only the central 30 degrees in both eyes. The anterior segment did not show any morphological changes. Optical coherence tomography revealed total absence of the photoreceptor layer of the retina outside the fovea, where a discoid remnant of cone photoreceptors could be detected. Neither setting of the standard full-field electroretinography could detect any electrical response from the retina. Color fundus photos presented peripheral chorioretinal atrophy and central RPE mottling. A hyperreflective parafoveal ring was detected on fundus autofluorescent photos, a characteristic sign of hereditary retinal dystrophies. CONCLUSIONS: To the best of our knowledge, this is the first report on the ophthalmological phenotype associating with a homozygous NEUROD1 null mutation in humans. Our results indicate that the loss of NEUROD1 has similar functional and anatomic consequences in the human retina as those described in mice. The present description can help the diagnosis of future cases and provide clues on the rate of disease progression.

Optical coherence tomography for biofilm detection in chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a multifactorial disease that seems to be associated with the presence of microbial biofilms and corresponding subepithelial inflammatory reactions. Optical coherence tomography (OCT) might be applied to detect bacterial and fungal biofilms in patients with CRSwNP. A total of 27 patients with CRSwNP undergoing endoscopic sinus surgery (ESS) were analyzed. The negative control group consisted of six patients undergoing septoplasty for nasal obstruction without CRSwNP. The nasal polyps and inferior turbinate mucosa specimens applied as negative controls were processed to OCT analysis and H.E. and Gram staining. Biofilm was detected in 22 of 27 patients (81.5 %) with CRSwNP and in none of six negative controls. In our series, OCT scan showed an obvious association with the findings of H.E. and Gram staining and was allocated to be a good predictor of biofilm existence. On OCT images, biofilms were displayed as distinct superficial layers with high optical density. It was found that microscopic architecture of biofilms was strongly associated with the integrity of nasal mucosa and to the cellular pattern of subepithelial inflammatory reaction. This study confirmed the presence of microbial biofilms in patients with CRSwNP according to OCT scans and histological analysis. Since biofilms may affect the severity and recurrence rate of CRS treated by ESS they should be detected preoperatively. In conclusion, single application of OCT analysis or combination with conventional histological protocols provides a robust and reliable method for the detection of bacterial and fungal biofilms in CRSwNP. Level of evidence 3b, individual case-control study.

Effect of the Gas6 c.834+7G>A polymorphism and the interaction of known risk factors on AMD pathogenesis in Hungarian patients.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95%CI: 0.26-0.97, p = 0.04). Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95%CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95%CI: 3.30-393.02, p = 0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95%CI: 1.98-12.25, p = 0.0006). Our results suggest a protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the pathogenesis of dry AMD.

Keratometry evaluations with the Pentacam high resolution in comparison with the automated keratometry and conventional corneal topography.

PURPOSE: To determine the reliability and repeatability of keratometry (K) measurements obtained with the Pentacam high resolution (HR), automated keratometry, and corneal topography systems. METHODS: The right eyes of 46 healthy subjects were examined prospectively. Keratometry measurements in the flat (Kf) and steep (Ks) meridians were taken by 2 independent investigators with the Pentacam HR (Oculus, Wetzlar, Germany) followed by automated keratorefractometry (KR-8100; Topcon, Tokyo, Japan), and corneal topography (TMS-4; Tomey, Erlangen, Germany). RESULTS: The mean K readings of the Pentacam HR, automated keratometry, and corneal topography were 43.40/43.34 diopter (D), 43.99/43.98 D, and 43.80/43.83 D, respectively. The difference between the values was statistically significant (P < 0.0001, repeated measures analysis of variance). Strong significant correlation was observed between the Pentacam HR and keratometry (Kf: r = 0.952/0.954; Ks: r = 0.845, Spearman rank test), and Pentacam HR and corneal topography (Kf: r = 0.933/0.930; Ks: r = 0.838/0.829) (P < 0.0001). No significant difference was presented between the 2 investigators for any of the instruments (P = 0.215-0.983). Moreover, high correlation was found between the K readings of the observers (interoperator intraclass correlation coefficients ranged from 0.95 to 0.99). CONCLUSIONS: The Pentacam HR provided reliable K measurements in clinical practice in comparison with an automated keratometer and a corneal topographer. Based on the results, for patient follow-up, one keratometry device is recommended.

Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients.

PURPOSE: Recent studies strongly support the role of genetic factors in the aetiology of age-related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors. METHODS: In a case-control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls. Detailed patient histories were recorded with the use of a questionnaire focusing on known risk factors for AMD. RESULTS: In the early AMD subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9-fold (95% confidence interval [CI] 1.7-14.2), 7.4-fold (95% CI 2.1-26.2) or 10.1-fold (95% CI 2.5-40.8) risk of disease, respectively. In the late AMD subgroup, carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7-fold (95% CI 3.7-31.0), 11.3-fold (95% CI 3.2-40.4) or 13.5-fold (95% CI 3.3-55.4) greater disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination conferred a 15.0-fold (95% CI 3.2-71.0) increase in risk, whereas two LOC387715 risk alleles combined with one CFH risk allele was associated with a 14.0-fold (95% CI 2.1-95.1) increased risk for late AMD. ApoE alleles neither increased disease risk nor proved to be protective. CONCLUSIONS: The CFH, LOC387715 and HTRA1 polymorphisms are strongly associated with the development of AMD in the Hungarian population. The association is particularly pronounced when homozygous risk alleles are present and in the late stages of the disease.

Clearance of dying ARPE-19 cells by professional and nonprofessional phagocytes in vitro- implications for age-related macular degeneration (AMD).

PURPOSE: Failure of retinal pigment epithelial (RPE) cells and macrophages to engulf different dying cells in the retina may result in accumulation of debris and development of age-related macular degeneration (AMD). The dynamics and influence of different treatments on this clearance process can be studied in vitro using human ARPE-19 cells and macrophages as phagocytes modelling dry and wet type of AMD, respectively. METHODS: Death through extracellular matrix detachment using polyHEMA-coated surfaces (anoikis) and UV irradiation (apoptosis) was induced in ARPE-19 cells. Two-coloured phagocytic assays were performed to quantify the amount of dying cells phagocytes engulfed (flow cytometry) and for visualization (fluorescent and scanning electron microscopy). The effect of phosphatidylserine inhibition with recombinant annexin-V and glucocorticoid (triamcinolone) treatment on the phagocytic process was tested. RESULTS: The clearance of anoikic and apoptotic cells by nondying ARPE-19 cells over 8 hr of co-incubation increased over time (at 8 hr, over 53% and 35% of the phagocytes contained engulfed dying cells, respectively). The human macrophages engulfed the anoikic and apoptotic ARPE-19 cells with seven and four times lower capacity, respectively. Phosphatidylserine appearance on the dying cells did not affect, but triamcinolone treatment enhanced the phagocytosis of the dying cells by macrophages. CONCLUSIONS: ARPE-19 cells are more efficient in clearing anoikic than UV-induced apoptotic cells. Macrophages are less efficient in the clearance process than ARPE-19 cells. The present model can be used for studying both dry and wet type of AMD in vitro and for testing different pharmacological aspects affecting this disease.

Assessment and reproducibility of anterior chamber depth measurement with anterior segment optical coherence tomography compared with immersion ultrasonography.

PURPOSE: To measure anterior chamber depth (ACD) with an anterior segment optical coherence tomography (AS-OCT) and a standard ultrasonic (US) axial scan (A-scan) device using an immersion technique and to assess repeatability, reproducibility, and correlations of the measurements. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Sixty healthy eyes of 41 patients were enrolled in a study. The central ACD was measured 5 times with AS-OCT (Visante, Carl Zeiss Meditec) using its chamber tool and 5 times with a US A-scan device (UltraScan Imaging System, Alcon Laboratories) using an immersion method. The measurements were performed consecutively by 2 independent observers. RESULTS: The mean ACD measured with AS-OCT was 3.12 mm +/- 0.33 (SD) by observer 1 and 3.11 +/- 0.33 mm by observer 2 (P = .78). The repeatability was 0.8% +/- 0.4% and 1.9% +/- 1.4%, respectively. The reproducibility was 0.23%. The reliability coefficient with AS-OCT was 99.6%. The mean ACD measured with immersion US A-scan was 2.98 +/- 0.33 mm by observer 1 and 2.95 +/- 0.34 mm by observer 2 (P = .68) . The repeatability was 6.4% +/- 3.8% by observer 1 and 8.5% +/- 4.9% by observer 2. The reproducibility was 0.88%. The reliability coefficient was 87.1% for US A-scan measurements. The difference between ACD values with AS-OCT and values with US A-scan was statistically significant (P = .02). The correlation (r) between AS-OCT and US A-scan was 0.732 (P<.0001) by observer 1 and 0.802 (P<.0001) by observer 2. CONCLUSIONS: Anterior chamber measurements were significantly deeper with AS-OCT than with US immersion A-scan. Repeatability of ACD measurements was better with AS-OCT than with immersion US, and reproducibility was equal with the 2 methods.

Anterior chamber depth measurements in phakic and pseudophakic eyes: Pentacam versus ultrasound device.

PURPOSE: To compare anterior chamber depth (ACD) measurements with a new optical device with those taken with a standard ultrasound (US) device in emmetropic phakic and pseudophakic eyes. SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: Forty-two phakic and 42 pseudophakic patients with normal axial lengths (mean 22.91 mm +/- 1.21 [SD]) were enrolled in the study. The ACD was measured 3 times with Scheimpflug-based Pentacam (Oculus) and then 3 times with a standard A-scan US device (AL-2000, Tomey). The data were then analyzed. RESULTS: In the phakic group, the mean ACD was 2.87 +/- 0.4 mm with the Pentacam and 2.89 +/- 0.49 mm with ultrasound A-scan (US) (P = .84). In the pseudophakic group, the mean ACD was 3.41 +/- 0.28 mm and 3.97 +/- 0.45 mm, respectively (P < .001). The correlation between measurements was significant in both the phakic and pseudophakic groups (r = .547/P < .001 and r = .404/P = .01, respectively). CONCLUSIONS: In phakic eyes, ACD measured with the Pentacam and with US was the same. However, in pseudophakic eyes, the difference was significantly lower when the ACD was measured with the Pentacam. Therefore, in pseudophakic patients, further evaluation of ACD data with the Scheimpflug-based system is necessary.

Comparison of central corneal thickness measurements with a new optical device and a standard ultrasonic pachymeter.

PURPOSE: To compare central corneal thickness (CCT) values obtained with ultrasonic pachymetry and a new optical method using partial coherence interferometry (PCI). SETTING: Department of Ophthalmology, Medical Health and Science Center, University of Debrecen, Debrecen, Hungary. METHODS: The study comprised 136 eyes of 70 patients whose spherical refractive error was not greater than +/-6.0 diopters (D) and whose keratometric astigmatism was not greater than 2.0 D. Central corneal thickness was measured 5 times with a new optical device (ACMaster, Zeiss) and with an ultrasonic pachymeter (AL-2000, Tomey). All measurements were obtained by the same investigator. RESULTS: Mean CCT was 531.2 microm +/- 3.9 (SD) with PCI and 547.8 +/- 36.0 microm with the ultrasonic device. The difference between groups was significant (P = .001). There was no difference between CCT values measured in right and left eyes (P = .55) with ultrasonography and PCI (P = .67). The coefficient variation was 0.73% for PCI and 6.5% for ultrasonography. Correlation between the CCT measurements with both devices was strong and statistically significant (Spearman correlation = .91, P = .001). CONCLUSIONS: Mean CCT values measured by the PCI method were significantly smaller than those measured by the ultrasonic device. Central corneal thickness measured with PCI is more reproducible and seems to be more reliable than that measured by ultrasonography.