Evaluation of Retinal Blood Flow in Patients with Monoclonal Gammopathy Using OCT Angiography.

BACKGROUND: Monoclonal gammopathy (MG) is characterized by monoclonal protein overproduction, potentially leading to the development of hyperviscosity syndrome. OBJECTIVE: To assess retinal circulation using optical coherence tomography angiography (OCTA) parameters in patients with monoclonal gammopathy. METHODS: OCTA measurements were performed using the Optovue AngioVue system by examining 44 eyes of 27 patients with MG and 62 eyes of 36 control subjects. Superficial and deep retinal capillary vessel density (VD SVP and DVP) in the whole 3 × 3 mm macular and parafoveal area, foveal avascular zone (FAZ) area, and central retinal thickness (CRT) were measured using the AngioAnalytics software. The OCTA parameters were evaluated in both groups using a multivariate regression model, after controlling for the effect of imaging quality (SQ). RESULTS: There was no significant difference in age between the subjects with monoclonal gammopathy and the controls (63.59 ± 9.33 vs. 58.01 ± 11.46 years; p > 0.05). Taking into account the effect of image quality, the VD SVP was significantly lower in the MG group compared to the control group (44.54 ± 3.22% vs. 46.62 ± 2.84%; p < 0.05). No significant differences were found between the two groups regarding the other OCTA parameters (p > 0.05). CONCLUSIONS: A decreased superficial retinal capillary vessel density measured using OCTA in patients with MG suggests a slow blood flow, reduced capillary circulation, and consequent tissue hypoperfusion. An evaluation of retinal circulation using OCTA in cases of monoclonal gammopathy may be a sensitive method for the non-invasive detection and follow-up of early microcirculatory dysfunction caused by increased viscosity.

The Effect of Circle of Willis Morphology on Retinal Blood Flow in Patients with Carotid Stenosis Measured by Optical Coherence Tomography Angiography.

The Circle of Willis (CoW) is the main collateral system, and its morphological variants are more common in patients who have severe carotid artery stenosis. Earlier data suggest that optical coherence tomography angiography (OCTA) may help to assess the changes in cerebral vascular perfusion by imaging the retinal blood flow. In this single-center prospective clinical study, patients scheduled for carotid endarterectomy (CEA) underwent preoperative computed tomography angiography (CTA) of the extra- and intracranial cerebral circulation. OCTA imaging was performed one week before surgery and postoperatively one month later. The patients were divided into two subgroups based on CTA evaluation of CoW: compromised CoW or non-compromised CoW (containing hypoplastic and normal segments). The effect of the patient's age, OCTA scan quality (SQ), CoW morphology, laterality, and surgery on superficial capillary vessel density (VD) in the macula were assessed in multivariable regression models using linear mixed models. We found that VD significantly decreased with aging (-0.12%; 95%CI: -0.07--0.15; p < 0.001) and was significantly higher in patients with non-compromised CoW morphology (by 0.87% 95%CI (0.26-1.50); p = 0.005). After CEA, retinal blood flow significantly improved by 0.71% (95%CI: 0.18-1.25; p = 0.01). These results suggest that in the case of carotid artery occlusion, patients with non-compromised CoW have more preserved ocular blood flow than subjects with compromised CoW due to remodeling of the intra-orbital blood flow. Measuring the retinal blood flow might be used as a relevant and sensitive indicator of collateral cerebrovascular circulation.

Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. METHODS: Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. RESULTS: Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity. CONCLUSION: Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy. TRIAL REGISTRATIONS: VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.

PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept. PATIENTS AND METHODS: Twenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 µl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system. RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 µg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 µg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 µg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95). CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Microbiota mitochondria disorders as hubs for early age-related macular degeneration.

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota-mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch's membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)-now called postbiotics-in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

The effect of systemic factors on retinal blood flow in patients with carotid stenosis: an optical coherence tomography angiography study.

Carotid artery stenosis (CAS) is among the leading causes of mortality and permanent disabilities in the Western world. CAS is a consequence of systemic atherosclerotic disease affecting the majority of the aging population. Optical coherence tomography angiography (OCTA) is a novel imaging technique for visualizing retinal blood flow. It is a noninvasive, fast method for qualitative and quantitative assessment of the microcirculation. Cerebral and retinal circulation share similar anatomy, physiology, and embryology; thus, retinal microvasculature provides a unique opportunity to study the pathogenesis of cerebral small vessel disease in vivo. In this study, we aimed to analyze the effect of systemic risk factors on retinal blood flow in the eyes of patients with significant carotid artery stenosis using OCT angiography. A total of 112 eyes of 56 patients with significant carotid stenosis were included in the study. We found that several systemic factors, such as decreased estimated glomerular filtration rate (eGFR), hypertension, and carotid occlusion have a significant negative effect on retinal blood flow, while statin use and carotid surgery substantially improve ocular microcirculation. Neither diabetes, clopidogrel or acetylsalicylic acid use, BMI, serum lipid level, nor thrombocyte count showed a significant effect on ocular blood flow. Our results demonstrate that a systematic connection does exist between certain systemic risk factors and retinal blood flow in this patient population. OCTA could help in the assessment of cerebral circulation of patients with CAS due to its ability to detect subtle changes in retinal microcirculation that is considered to represent changes in intracranial blood flow.

Pachychoroid diseases / Pachychorioidealis kórképek.

The aim of this study is to present our knowledge about pachychoroid diseases using case reports, literature review and our own clinical experiences. A summary flow chart of treatment options for the subgroups was prepared, too. Pachychoroid diseases include the following: central serous chorioretinopathy (CSCR), pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), peripapillary pachychoroid syndrome (PPS), focal choroidal excavation (FCE). A common feature of pachychoroid diseases is the quantitative or qualitative abnormality of the choroidea, which is often associated with subretinal fluid accumulation. The disease group does not currently have a standard treatment protocol; some of the multiple treatments prove to be more effective, however, there are significant differences between the subgroups. We summarize which subgroup benefits from eplerenone tablet therapy, micropulse laser therapy, verteporfin photodynamic therapy or intravitreal anti-VEGF injection therapy. Orv Hetil. 2020; 162(20): 770-781.

Differences in guidelines for patients with carotid artery stenosis in some European countries / A nyaki veroér-szukületes betegek ellátási irányelveinek különbségei Európa különbözo országaiban.

Összefoglaló. A tudomány jelenlegi állása szerint - csoportok összehasonlítására épülo matematikai-statisztikai eszközökkel - a leginkább hatékonynak és hatásosnak vélt kezelési módszerek szisztematikus elemzése mentén, a bizonyítékokon alapuló irányelveken nyugvó gyógyító munkát tekintjük követendonek. A nyaki veroérszukület ellátása esetén az utóbbi években elkészült mind a hazai, mind az európai irányelv, mindemellett a társszakmák irányelveiben is megjelentek kezelési javaslatok. Közleményünkben összehasonlítottuk a témában publikált magyar, angol, német és olasz nyelvu, valamint az európai társaságok által kiadott irányelveket. Az irányelvek alapelveikben hasonlóak, formailag és tartalmilag azonban jelentos (idonként egymásnak ellentmondani látszó) különbségeket találhatunk. Az ellentmondások három leggyakoribb oka: 1) az egyes irányelvek által kituzött célok különbözosége, 2) az aszimptomatikus és szimptomatikus betegcsoport definíciói, valamint 3) az eltéro evidenciaszintek. Az irányelvek összevetése alapján a tünetes, szignifikáns nyaki veroérszukületek sebészi ellátása evidenciának tekintheto. A szimptomatikus nyaki veroérszukület a definíció szerint ellenoldali cerebralis ischaemia okozta, tranziens vagy definitív plegia, paresis, aphasia és az azonos oldali arteria centralis retinae embolisatiója miatti amaurosis fugax. A tünetmentes nyaki veroérszukületek ellátása tekintetében az európai és a nemzeti irányelvek nem azonosak, ezen esetek terápiás döntése egyéni mérlegelést igényel. Tünetmentes, 70%-os stenosis esetén vascularteam-konzílium javasolt. Orv Hetil. 2020; 161(51): 2139-2145. Summary. The correct practice is the one that is proven to be the most effective based on systematic statistical analyses of different treatment methods, and is applied according to evidence-based principles. In recent years, not only has the European Society of Vascular Surgery created a guideline about the management of supra-aortic steno-occlusive disease, but some nations' vascular surgical societies and related disciplines have also developed their own guidance. In this paper, the guidelines by the European societies on the clinical care of patients with carotid artery luminal narrowing is compared to national guidelines published in Hungarian, English, German, and Italian. Although the fundamental points of the guidelines are similar, there are some important differences among them both in presentation and in content; as a result, they sometimes appear to be contradictory. The three main sources of inconsistency are the various goals, the discrepancy in the definition of symptomatic and asymptomatic carotid artery stenosis, and the bias arising from the use of distinct evidence levels. A comparison of guidelines suggests that the treatment of symptomatic significant carotid artery stenosis with surgery can be considered evidence. Symptomatic carotid artery stenosis is defined as transient or definite plegia, paresis, aphasia due to cerebral ischemia, and monocular blindness caused by embolism in the central retinal artery. However, in the case of asymptomatic 70% or greater carotid artery stenosis, the guidelines are quite heterogeneous, and these patients require individual consideration and a vascular team decision is recommended. Orv Hetil. 2020; 161(51): 2139-2145.

First experiences with Navilas® 577s micropulse laser in the treatment of diabetic maculopathy / Elso tapasztalataink diabeteses maculopathia Navilas® 577s mikropulzuslézer-készülékkel történo kezelésével.

Összefoglaló. Bevezetés és célkituzés: A Navilas® 577s mikropulzuslézerrel végzett kezelés biztonságosságának és hatásosságának vizsgálata diabeteses maculaoedemában. Módszer: Retrospektív vizsgálatunkba diabeteses maculaoedema miatt gondozott és legalább 6 hónapos utánkövetéssel rendelkezo, korábban Navilas® 577s mikropulzuslézer-kezelésen átesett 28 beteg 46 szemét válogattuk be. Minden szemen optikaikoherencia-tomográfia (OCT) vastagsági térkép navigált, nonkontakt, küszöb alatti mikropulzuslézer-kezelés történt egy alkalommal. A kezelést megelozoen és az azt követo 6. hónapban rögzítettük a látóélesség, a centrális retinavastagság értékeit és az éreredetu endothelialis növekedési faktort (VEGF) gátló injekciók számát. A követési ido végén megvizsgáltuk a szemfenéki képnek a digitális fundusfotográfia és az átmetszeti OCT-képek segítségével észlelheto változásait. Eredmények: A vizsgált szemek közül 30 esetben a lézerkezelést korábbi centrális maculaoedema miatt VEGF-gátló injekciós kezelés elozte meg, míg 16 szem esetében primer lézerkezelés történt. A Navilas® 577s mikropulzuslézer-kezelést követoen 6 hónappal sem a látóélesség, sem a centrális maculavastagság nem változott szignifikánsan egyik csoportban sem (p>0,05). Ugyanakkor a korábban injekciós kezelésben részesült szemek esetében a lézerkezelést megelozo 6 hónapban adott injekciók száma az átlagos 2,63 ± 1,18 értékrol átlagosan 0,5 ± 0,73 értékre csökkent (p<0,001). A fundusfotókon és az átmetszeti OCT-scaneken a lézerkezelést követoen egyetlen szem esetében sem találtunk látható pigmentelváltozásokat vagy hegesedést. Következetetés: Megfigyeléseink szerint a Navilas® 577s mikropulzuslézer-kezelés biztonságos a diabeteses maculaoedemás betegek kezelésében, továbbá a VEGF-gátlóval kezelt szemeken szerepet játszhat az injekciók számának csökkentésében. Orv Hetil. 2020; 161(49): 2078-2085. INTRODUCTION AND OBJECTIVE: To assess the safety and efficacy of Navilas® 577s micropulse subthreshold laser in the treatment of non-center involved diabetic macular edema. METHOD: In this retrospective study, we included 46 eyes of 28 patients with diabetic macular edema, who were treated at least 6 months ago with Navilas® 577s micropulse laser. Laser treatment was navigated by optical coherence tomography (OCT) macular thickness map in subthreshold micropulse mode at one occasion. Data from visual acuity testing, retinal thickness, and the number of anti-vascular endothelial growth factor (VEGF) injections needed 6 months before and after treatment were registered. At the end of the follow-up, digital fundus photography and OCT radial scans were performed to evaluate any possible anatomical changes. RESULTS: 30 eyes had previous anti-VEGF treatment for central macular edema, and in 16 eyes we performed the laser as primary treatment. At the end of the follow-up, no significant visual acuity or central retinal thickness change were observed (p>0.05). On the other hand, in the anti-VEGF pretreated group the number of injections decreased significantly from 2.63 ± 1.18 to 0.5 ± 0.73 (p<0.001). We did not find any pigmentary changes or visible signs of scaring on final fundus photography pictures or OCT radial scans. CONCLUSION: Navilas® 577s subthreshold microsecond laser proved to be a safe option in the treatment of diabetic macular edema. It can be very useful in anti-VEGF treated eyes by decreasing the number of injections needed. Orv Hetil. 2020; 161(49): 2078-2085.

Adverse ocular effects to systemic drug therapy / Szisztémás gyógyszerek szemészeti mellékhatásai

Systemic medications of various diseases can have adverse effects on the eye that range from asymptomatic lesions to potentially blinding complications such as toxic retinopathy and optic neuropathy. In the course of ophthalmological screening, with the early detection of toxic effects, the majority of drug-induced eye disorders can be prevented and even be reversed. Our review focuses on major drugs with common and significant ocular side effects. Physicians prescribing medications need to be keenly aware of ocular toxicity risks and the importance of regular screening. Orv Hetil. 2020; 161(23): 951-961.

Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions.

Aging of the microcirculatory network plays a central role in the pathogenesis of a wide range of age-related diseases, from heart failure to Alzheimer's disease. In the eye, changes in the choroid and choroidal microcirculation (choriocapillaris) also occur with age, and these changes can play a critical role in the pathogenesis of age-related macular degeneration (AMD). In order to develop novel treatments for amelioration of choriocapillaris aging and prevention of AMD, it is essential to understand the cellular and functional changes that occur in the choroid and choriocapillaris during aging. In this review, recent advances in in vivo analysis of choroidal structure and function in AMD patients and patients at risk for AMD are discussed. The pathophysiological roles of fundamental cellular and molecular mechanisms of aging including oxidative stress, mitochondrial dysfunction, and impaired resistance to molecular stressors in the choriocapillaris are also considered in terms of their contribution to the pathogenesis of AMD. The pathogenic roles of cardiovascular risk factors that exacerbate microvascular aging processes, such as smoking, hypertension, and obesity as they relate to AMD and choroid and choriocapillaris changes in patients with these cardiovascular risk factors, are also discussed. Finally, future directions and opportunities to develop novel interventions to prevent/delay AMD by targeting fundamental cellular and molecular aging processes are presented.

Ocular mucous membrane pemphigoid: a review.

Ocular mucous membrane pemphigoid (MMP) is a rare, immuno-mediated chronic progressive condition of the conjunctiva characterized by blisters developing from sub-epithelial tissue through disruption of the adhesions between the conjunctival epithelium and the sub-epithelium. Patients with ocular MMP, in many cases, develop profound conjunctival scarring and visual impairment. Furthermore, ocular MMP may lead to a progressive secondary corneal vascularization and to corneal opacification. Ocular MMP is difficult to diagnose during the initial stages because of false negatives during biopsy and variability in the clinical presentation. Most of the current pharmacological treatments aim to control the inflammatory response to reduce the progressive tissue remodeling which leads to the formation of a fibrotic scar. The course and prognosis of ocular MMP depend on the severity and progression of the disease after systemic immunomodulatory therapy. The aim of this review is to provide a comprehensive analysis of the current literature on established and emerging concepts in ocular MMP, with special attention to its clinical presentation, diagnosis, treatment, and pathogenic mechanisms, including the role of some cytokines and growth factors in the development of the disease.

Application of Correlation-Based Scoring Scheme for Visual Acuity Measurements in the Clinical Practice.

PURPOSE: Visual acuity tests are generally performed by showing eye charts to the subjects and registering their correct/incorrect identifications for the presented optotypes. We recently developed a correlation-based scoring method that significantly reduces the statistical error associated with relative letter legibility. In this paper, our purpose was to demonstrate the advantages and clinical utility of our scoring scheme compared to standard methods. METHODS: We developed a new computer-controlled measurement setup aligned with the ophthalmological standard. With this system, we presented the application of our correlation-based scoring in conventional clinical environment for 25 subjects and estimated the systematic error of the obtained acuity values. A separate experiment was performed by 14 additional subjects to reveal the test-retest variability of the new scoring method. RESULTS: The average systematic error relative to standard probability-based scoring is 0.01 logMAR over the examined subject group. Application of the correlation-based scheme when used in clinical environment with five letters per size decreases the repeatability error by ∼20% and increases diagnosis time by ∼10%. CONCLUSIONS: The new scoring scheme is directly applicable in clinical practice providing unbiased results with improved repeatability compared to standard visual acuity measurements. It reduces test-retest variability by the same amount as if the number of letters was doubled in traditional tests. TRANSLATIONAL RELEVANCE: Our new method is a promising alternative to conventional acuity tests in cases when high-precision measurements are required, for example evaluating implanted intraocular lenses, testing subjects with retinal diseases or cataract, and refractive surgery candidates.

[Ocular manifestations and management of Fusarium and Sarocladium infections]. / Fusarium és Sarocladium okozta fertozések szemészeti vonatkozásai és azok kezelése.

Since 2017, the nomenclature of Fusarium, Acremonium and Sarocladium species have changed, as these morphologically homogeneous, but phylogenetically heterogeneous species and species complexes may be differentiated using MALDI-TOF MS examination, analyzing nucleotic sequences. This resulted in taxonomical changes. We summarize the clinical course, diagnostic and therapeutic options of keratitis caused by Fusarium and Sarocladium. The challenge of Fusarium and Sarocladium keratitis management for an ophthalmologist lies in delayed diagnosis and therapy, fulminant progression and penetration of the Descemet's membrane, restricted availability, poor penetration of antifungal agents and therapy resistance. The diagnosis is based on the clinical history of corneal trauma or contact lens wear, PCR and MALDI-TOF MS, confocal microscopic examination, microbiological culture and light-microscopic analysis of corneal scrapings. As primary conservative treatment, 5% natamycin eye drops have to be used and with results of an antimycogram, topical 1% voriconazole or 0.15-0.25% amphotericin B, in some cases 0.02% polyhexamethylene-biguanide (PHMB) may be applied. Fusarium keratitis may benefit from additional 2 × 200 mg oral voriconazole treatment, daily. In therapy resistant cases, early, large diameter penetrating keratoplasty (PKP) has to be performed, with complete removal of the infected area. With late diagnosis, delayed specific treatment and surgery, mycotic hyphae may penetrate the Descemet's membrane, leading to the loss of vision and enucleation in about every fourth patient. In our paper, we also present the heterogeneous clinical history of five Fusarium and Sarocladium keratitis cases. Orv Hetil. 2019; 160(1): 2-11.

Effect of Spherical Aberration on the Optical Quality after Implantation of Two Different Aspherical Intraocular Lenses.

PURPOSE: To compare the effect of spherical aberration on optical quality in eyes with two different aspherical intraocular lenses. METHODS: 120 eyes of 60 patients underwent phacoemulsification. In patients' eyes, an aberration-free IOL (Aspira-aA; Human Optics) or an aberration-correcting aspherical IOL (Tecnis ZCB00; Abott Medical Optics) was randomly implanted. After surgery, contrast sensitivity and wavefront measurements as well as tilt and decentration measurements were performed. RESULTS: Contrast sensitivity was significantly higher in eyes with Aspira lens under mesopic conditions with 12 cycles per degree (CPD) and under photopic conditions with 18 CPD (p = 0.02). Wavefront measurements showed a higher total spherical aberration with a minimal pupil size of 4 mm in the Aspira group (0.05 ± 0.03) than in the Tecnis group (0.03 ± 0.02) (p = 0.001). Strehl ratio was higher in eyes with Tecnis (0.28 ± 0.17) with a minimal pupil size larger than 5 mm than that with Aspira (0.16 ± 0.14) (p = 0.04). In pupils with a minimum diameter of 4 mm spherical aberration had a significant effect on Strehl ratio, but not in pupils with a diameter less than 4 mm. CONCLUSIONS: Optical quality was better in eyes with the aberration-correcting Tecnis IOL when pupils were large. In contrast, this could not be shown in eyes with pupils under 4 mm or larger. This trial is registered with Clinicaltrials.gov NCT03224728.

Accuracy of machine learning classifiers using bilateral data from a Scheimpflug camera for identifying eyes with preclinical signs of keratoconus.

PURPOSE: To describe the topographic and tomographic characteristics of normal fellow eyes of unilateral keratoconus cases and to evaluate the accuracy of machine learning classifiers in discriminating healthy corneas from the normal fellow corneas. SETTING: Department of Ophthalmology, Semmelweis University, Budapest, Hungary. DESIGN: Retrospective case-control study. METHODS: Patients with bilateral keratoconus (keratoconus group), clinically and according to the keratoconus indices of the Pentacam HR Scheimpflug camera; normal fellow eyes of patients with unilateral keratoconus (fellow-eye group); and eyes of refractive surgery candidates (control group) were compared. Tomographic data, topographic data, and keratoconus indices were measured in both eyes using the Scheimpflug camera. Receiver operating characteristic (ROC) analysis was used to assess the performance of automated classifiers trained on bilateral data as well as individual parameters to discriminate fellow eyes of patients with keratoconus from control eyes. RESULTS: Keratometry, elevation, and keratoconus indices values were significantly higher and pachymetry values were significantly lower in keratoconus eyes than in fellow eyes of unilateral keratoconus cases (P < .001). These fellow eyes had significantly higher keratometry, elevation, and keratoconus index values and significantly lower pachymetry values than control eyes (P < .001). Automated classifiers trained on bilateral data of index of height decentration had higher accuracy than the unilateral single parameter in discriminating fellow eyes of patients with keratoconus from control eyes (area under ROC 0.96 versus 0.88). CONCLUSION: Automatic classifiers trained on bilateral data were better than single parameters in discriminating fellow eyes of patients with unilateral keratoconus with preclinical signs of keratoconus from normal eyes. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1ß within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes.

OCULAR WAVEFRONT ABERRATIONS AND OPTICAL QUALITY IN DIABETIC MACULAR EDEMA.

PURPOSE: To evaluate optical quality and internal aberrations in patients with diabetic macular edema. METHODS: In this prospective study, 33 eyes of patients with diabetic macular edema were scanned with a ray-tracing wavefront device. As a control group, wavefront aberrometry was performed in 31 patients. Ocular and internal aberrations and visual quality metrics were evaluated separately to determine whether the source of aberrations was ocular or internal. Main outcome measures included corrected visual acuities, ocular and internal aberrations, Strehl ratio, and modulation transfer function. RESULTS: There was a statistically significant difference between the groups in internal higher order (HO) root mean square (0.34 ± 0.24 vs. 0.16 ± 0.05), HO Strehl ratio (0.08 ± 0.05 vs. 0.18 ± 0.09), and modulation transfer function (0.29 ± 0.1 vs. 0.4 ± 0.1). There was no statistically significant difference in Strehl ratio and HO root mean square between phakic and pseudophakic patients. Height of cystoid spaces was a significant predictor (P < 0.001) of Strehl ratio. Besides inner and outer segment integrity, HO Strehl ratio significantly determined best-corrected visual acuity. CONCLUSION: In eyes with macular edema, internal HO wavefront aberrations were greater than in control eyes. This increase in HO wavefront error seems visually relevant. This study results suggest increased intraretinal edema as the source of HO aberrations.

[Results of femtosecond laser-assisted cataract surgery using the new 2.16 software and the SoftFit® Patient Interface]. / A femtoszekundumlézer-asszisztált szürkehályog-mutét eredményei az új 2.16-os szoftverrel és a módosított SoftFit® páciensi felszínnel.

INTRODUCTION: Femtosecond laser-assisted cataract surgery improved the results of cataract surgeries. AIM: Outcome analysis of femtosecond laser-assisted cataract surgery using the novel 2.16 software and the SoftFit(®) Patient Interface. METHOD: The novel software and the newly developed Patient Interface were used in 100 eyes of 100 patients. RESULTS: Length of femtosecond laser pretreatment decreased to 45-60 seconds. The smaller size of the new patient interface resulted in easier docking even on pediatric eyes. Suction force used for docking decreased from 40-50 mmHg to 16-20 mmHg. Incidence rate of subconjunctival suffusion decreased from 40% to 15-20% and its clinical severity was reduced, too. No corneal microfolds evolved, thus the incidence rate of the free-floating capsulotomies increased from 30% to 97%. The total energy of femtosecond laser pretreatment was decreased by almost 50%. Corneal wounds had the desired structure, and they were easy to open and closed precisely. CONCLUSIONS: The SoftFit(®) patient interface and the novel software widened the possible uses of the femtosecond laser-assisted cataract surgery, e.g. in pediatric ophthalmology. Innovations improved the safety and the predictability of the method.

Changes of corneal topography indices after CXL in progressive keratoconus assessed by Scheimpflug camera.

PURPOSE: To evaluate the accuracy of Scheimpflug camera topography indices in detecting the therapeutic effect of corneal collagen cross-linking (CXL) on progressive keratoconus in the long term. METHODS: Fifty eyes of 25 patients with keratoconus were enrolled. CXL was performed in 25 eyes with progressive keratoconus (CXL group) and 25 fellow eyes with nonprogressive keratoconus served as controls. Thinnest corneal thickness, anterior keratometry (flat, steep), and keratoconus indices were measured with Scheimpflug camera before and 12 to 25 months after CXL. Regression analysis was used to evaluate the influence of corneal thickness and follow-up time on flattening effect of CXL. RESULTS: At baseline, steep keratometric values were significantly higher and thinnest corneal thickness values were lower in the CXL group (P = .027, .034), parallel with increased values of keratoconus indices: index of surface variance (P = .013), index of vertical asymmetry (P = .038), keratoconus index (P = .019), center keratoconus index (P = .039), index of height asymmetry (P = .037), index of height decentration (P = .0016), and radius minimum (P = .008). After adjustment for thinnest corneal thickness and follow-up time, CXL showed significant flattening effect expressed by changes in radius minimum (P < .001), index of surface variance (P = .03), keratoconus index (P = .006), center keratoconus index (P = .03), and index of height asymmetry (P = .026). Thinnest corneal thickness had significant influence on changes of index of surface variance (P = .049), index of vertical asymmetry (P = .01), and center keratoconus index (P = .03). Follow-up time showed no significant influence in any models (P > .05). CONCLUSIONS: Topographic indices indicate corneal flattening after CXL in the long term. Monitoring keratoconus index and index of height asymmetry should be the preferred choice in daily clinical practice because changes in values of these indices are independent from initial corneal thickness.