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.

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.

Ocular signs and comorbidities in monoclonal gammopathy: Analysis of 84 eyes of 42 subjects / A monoklonális gammopathia szemészeti jelei és szövodményei: 42 beteg 84 szemének vizsgálata

Összefoglaló. Célkituzés: A monoklonális gammopathia szemészeti jeleinek és szövodményeinek vizsgálata. Betegek és módszerek: Két nagy budapesti hematológiai ellátóhely 1999 és 2020 között diagnosztizált és/vagy kezelt, monoklonális gammopathiát mutató betegeit vizsgáltuk (42 beteg 84 szeme, 42,86% férfi; átlagéletkor 63,83 ± 10,76 év). A hematológiai diagnózis 3 esetben bizonytalan jelentoségu monoklonális gammopathia, 34 esetben myeloma multiplex, 3 esetben parázsló myeloma, 1-1 esetben Waldenström-macroglobulinaemia és amyloidosis voltak. Kontrollcsoportként véletlenszeruen kiválasztott, hasonló korcsoportú, hematológiai betegség nélküli egyéneket vizsgáltunk (43 beteg 86 szeme, 32,56% férfi; átlagéletkor 62,44 ± 11,89 év). A szemészeti vizsgálat elott minden személy kitöltötte a Szemfelszíni Betegség Index (OSDI-) kérdoívet. A szemészeti vizsgálat során a látóélesség vizsgálata mellett pupillatágítást követoen réslámpás vizsgálatot végeztünk. Eredmények: Monoklonális gammopathiában az OSDI-érték szignifikánsan magasabb volt, mint a kontrollokban (p = 0,002). Gammopathiában 3 beteg 5 szeménél (5,95%) találtunk potenciális szaruhártya-immunglobulinlerakódást. Gammopathiában szárazszem-betegség 66,67%-ban, szürke hályog 55,95%-ban, Meibom-mirigy-diszfunkció 20,24%-ban, hátsó kérgi szürke hályog 19,05%-ban, egyéb szaruhártyahegek és -homályok 17,86%-ban, krónikus szemhéjgyulladás 14,29%-ban, szemészeti eltérés hiánya 11,90%-ban, macula- és/vagy retinadrusen 9,52%-ban, szaruhártya-immunglobulinlerakódás 5,95%-ban, epiretinalis membrán 5,95%-ban, korábbi szürkehályog-mutét 5,95%-ban, glaucoma 4,76%-ban, Fuchs-dystrophia 2,38%-ban, perifériás retinadegeneráció 2,38%-ban, chorioidea naevus 2,38%-ban, diabeteses retinopathia 1,19%-ban, arteria centralis retinae elzáródás 1,19%-ban, vena centralis retinae ágelzáródás 1,19%-ban, amblyopia 1,19%-ban volt kimutatható. A szárazszem-betegség (p = 0,002), a hátsó kérgi szürke hályog (p = 0,001), a szürke hályog (p<0,00001) és az egyéb szaruhártyahegek és -homályok (p = 0,01) szignifikánsan magasabb arányban fordultak elo a monoklonális gammopathiát mutató betegekben, mint a kontrollokban. Következtetés : Monoklonális gammopathiában a szárazszem-betegség és a szürke hályog a leggyakoribb szemészeti eltérés. A monoklonális gammopathia potenciális szemészeti jelei és szövodményei miatt javasoljuk a betegek évenkénti szemészeti ellenorzését, életminoségük javítása érdekében. Orv Hetil. 2021; 162(38): 1533-1540. OBJECTIVE: To examine ocular signs and ocular comorbidities in monoclonal gammopathy. PATIENTS AND METHODS: We analyzed patients from two large referral hematology centers in Budapest, who were diagnosed and/or treated with monoclonal gammopathy between 1997 and 2020 (84 eyes of 42 patients, 42.86% male, mean age 63.83 ± 10.76 years). Before the ophthalmic examination, the subjects filled in the Ocular Surface Disease Index (OSDI) questionnaire. Ophthalmic examination included visual acuity test and slit-lamp examination following dilation of the pupil. RESULTS: OSDI scores were significantly higher in subjects with monoclonal gammopathy than in controls (p = 0.002). Among gammopathy subjects, we observed potential corneal immunoglobulin deposition in 5 eyes of 3 patients (5.95%). In gammopathy subjects, there was dry eye disease (66.67%), cataract (55.95%), Meibomian gland dysfunction (20.24%), posterior cortical cataract (19.05%), corneal scars and degenerations (17.86%), chronic blepharitis (14.29%), absence of ocular complaint (11.90%), macular or retinal drusen (9.52%), corneal immunoglobulin deposition (5.95%), epiretinal membrane (5.95%), previous cataract surgery (5.95%), glaucoma (4.76%), Fuchs dystrophy (2.38%), peripheral retinal degeneration (2.38%), chorioideal naevus (2.38%), diabetic retinopathy (1.19%), central retinal artery occlusion (1.19%), central retinal vein branch occlusion (1.19%) and amblyopia (1.19%). The proportion of dry eye disease (p = 0.002), posterior cortical cataract (p = 0.001), cataract (p<0.00001), and corneal scars and degenerations (p = 0.01) were significantly higher in gammopathy subjects than in controls. CONCLUSION: Dry eye disease and cataracts are the most common ocular comorbidities in patients with monoclonal gammopathy. Therefore, due to the potential ocular signs and comorbidities of monoclonal gammopathy, we suggest a regular, yearly ophthalmic checkup of these patients to improve their quality of life. Orv Hetil. 2021; 162(38): 1533-1540.

Ocular Signs and Ocular Comorbidities in Monoclonal Gammopathy: Analysis of 80 Subjects.

PURPOSE: To examine the ocular signs of monoclonal gammopathy and to evaluate ocular comorbidities in subjects with monoclonal gammopathy. Patients and Methods. We analyzed patients from two large referral hematology centers in Budapest, diagnosed and/or treated with monoclonal gammopathy between 1997 and 2020. As a control group, randomly selected individuals of the same age group, without hematological disease, have been included. There were 160 eyes of 80 patients (38.75% males; age 67.61 ± 10.48 (range: 38-85) years) with monoclonal gammopathy and 86 eyes of 43 control subjects (32.56% males; age 62.44 ± 11.89 (range 37-86) years). The hematological diagnosis was MGUS in 9 (11.25%), multiple myeloma in 61 (76.25%), smoldering myeloma in 6 (7.50%), and amyloidosis or Waldenström macroglobulinemia in 2 cases (2.50%-2.50%). Before detailed ophthalmic examination with fundoscopy, 42 subjects with gammopathy (52.50%) and all controls filled the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: The OSDI score and best-corrected visual acuity (BCVA) were significantly worse in subjects with monoclonal gammopathy than in controls (p=0.02; p=0.0005). Among gammopathy subjects, we observed potential corneal immunoglobulin deposition in 6 eyes of 4 (3.75%) patients. Ocular surface disease (p=0.0001), posterior cortical cataract (p=0.01), and cataract (p=0.0001) were significantly more common among gammopathy subjects than in controls (χ 2 test). CONCLUSIONS: Ocular surface disease and cataract are more common, and BCVA is worse in patients with monoclonal gammopathy than in age-matched controls. Therefore, and due to the potential ocular signs and comorbidities of monoclonal gammopathy, we suggest a regular, yearly ophthalmic checkup of these patients to improve their quality of life.

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.

[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.

[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.