Examination of Subbasal Nerve Plexus and Central Corneal Stromal Microstructure in Subjects With Congenital Aniridia, Using in Vivo Confocal Laser Scanning Microscopy.

PURPOSE: During life up to 70% of aniridia subjects develop aniridia-associated keratopathy (AAK). AAK is characterized by limbal stem cell insufficiency, impaired corneal epithelial cell differentiation and abnormal cell adhesion, which leads to centripetal spreading vascularization, conjunctivalization, and thickening of the cornea. Our aim was to examine the subbasal nerve plexus and central corneal stromal microstructure in subjects with congenital aniridia, using in vivo confocal laser scanning microscopy CLSM. METHODS: 31 eyes of 18 patients (55.6% males, mean age: 25.22 ± 16.35 years) with congenital aniridia and 46 eyes of 29 healthy subjects (41.4% males, mean age 30 ± 14.82 years) were examined using the Rostock Cornea Module of Heidelberg Retina Tomograph-III. At the subbasal nerve plexus, corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), and corneal nerve fiber width (CNFW) were analyzed using ACCMetrics software. Keratocyte density in the anterior, middle and posterior stroma was assessed manually. RESULTS: The CNFD (2.02 ± 4.08 vs 13.99 ± 6.34/mm2), CNFL (5.78 ± 2.68 vs 10.56 ± 2.82 mm/mm2) and CTBD (15.08 ± 15.62 vs 27.44 ± 15.05/mm2) were significantly lower in congenital aniridia subjects than in controls (p < 0.001 for all). CNFW was significantly higher in aniridia subjects than in controls (0.03 ± 0.004 vs 0.02 ± 0.003 mm/mm2) (p = 0.003). Keratocyte density was significantly lower in all stromal layers of aniridia subjects than in controls (p < 0.001 for all). Stromal alterations included confluent keratocytes, keratocytes with long extensions and hyperreflective dots between keratocytes in aniridia. CONCLUSIONS: Decrease in CNFD, CNFL, and CTBD, as well as increase in CNFW well refer to the congenital aniridia-associated neuropathy. The decreased keratocyte density and the stromal alterations may be related to an increased cell death in congenital aniridia, nevertheless, stromal changes in different stages of AAK have to be further analyzed in detail.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis-With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups.

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease.

[Congenital aniridia patients' experience on their visual impairment in Hungary.] / Veleszületett aniridiás betegek látáskárosodással kapcsolatos tapasztalatai Magyarországon.

INTRODUCTION: Aniridia is a rare congenital panocular disease associated with varying degrees of visual acuity impairment. OBJECTIVE: To assess the experiences of congenital aniridia patients in Hungary, with visual impairment using a questionnaire developed by the ANIRIDIA-NET. PATIENTS AND METHOD: Patients completed the Hungarian version of the 20-item ANIRIDIA-NET questionnaire with our assistance. The questionnaire covered demographic data, the most common complaints caused by the disease, the difficulties caused by low vision in different life situations and the frequency of low vision aids used in daily life. RESULTS: 33 subjects (17 female [51.51%] and 16 male [48.48%]), 16 (48.5%) children and 17 (51.5%) adults completed the questionnaire, with an age of 25.69 ± 17.49 years (5-59 years). Daily photosensitivity was reported by 27 (81.8%), dry eyes by 5 (15.2%), tearing by 4 (12.1%), fluctuating vision by 3 (9.1%), and eye pain by 2 (6.1%) subjects. The majority of respondents said that personal communication with schoolmates (16 [48.5%]) or colleagues at work (11 [33.3%]) never caused difficulties because of their visual impairment. 29 people (87.9%) never needed help with daily routines at home, 24 (72.7%) with getting to school/work and 17 (51.5%) with various activities. 29 people (87.8%) never used low vision aids for communication, 23 (69.7%) for travelling, 20 (60.6%) for participating in social activities, 18 (54.5%) for studying/work. CONCLUSION: Although aniridia is associated with reduced visual acuity, the majority of people with congenital aniridia, especially in childhood, manage to cope with personal communication and various life situations without difficulty, despite their eye complaints. Low vision aids can be an important aid for them as they grow into adulthood and as they age. Orv Hetil. 2023; 164(34): 1342-1349.

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.

[Staging of aniridia-associated keratopathy]. / Az aniridiához társult keratopathia stádiumbeosztása.

INTRODUCTION: Congenital aniridia is a rare panocular disease that affects almost all eye structures leading in most patients to reduced visual acuity. Ophthalmological signs include aniridia-associated keratopathy, secondary glaucoma, cataract, macular and optic nerve head hypoplasia, nystagmus. Although the term aniridia-associated keratopathy has long been used in the literature, various staging proposals have been described. OBJECTIVE: To analyze aniridia-associated keratopathy stages, using available literature classifications, in patients with aniridia in Hungary. PATIENTS AND METHODS: We examined 65 eyes of 33 patients with congenital aniridia (age: 25.69 ± 17.49 [5-59] years, 17 females [51.51%]). We recorded the corneal status by slit-lamp examination and classified the corneal abnormalities according to the Mackman, Mayer, López-García and Lagali staging. RESULTS: According to Mackman's classification, 8 eyes (12.3%) were in stage 0, 0 eye in stage 1A, 38 eyes (58.46%) in stage 1B and 19 eyes (29.23%) in stage 2. According to Mayer, stage I included 8 eyes (12.3%), stage II 38 eyes (58.46%), stage III 5 eyes (7.7%), stage IV 7 eyes (10.77%) and stage V 7 eyes (10.77%). In López-García's classification, 8 eyes (12.3%) could not be grouped, 20 eyes (30.77%) were in stage 1, 18 eyes (27.7%) in stage 2 and 19 eyes (29.3%) in stage 3. Lagali's classification included 8 eyes (12.3%) in stage 0, 20 eyes (30.77%) in stage 1, 18 eyes (27.7%) in stage 2, 5 eyes (7.7%) in stage 3 and 14 eyes (21.54%) in stage 4. CONCLUSION: We recommend using Lagali's staging scheme for aniridia-associated keratoptahy due to its ease of use, detailed progression assessment, and treatment planning. In stage 1 according to Lagali, blood vessels cross the limbus by up to 1 mm, in stage 2 the central 2-3 mm of the corneal area is spared of blood vessels. When the blood vessels reach the center of the cornea, it is stage 3, followed by opaque, uneven corneal pannus in stage 4. Orv Hetil. 2023; 164(27): 1063-1069.

Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.

Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus.

Evidence of Disruption in Neural Regeneration in Dry Eye Secondary to Rheumatoid Arthritis.

The purpose of our study was to analyze abnormal neural regeneration activity in the cornea through means of confocal microscopy in rheumatoid arthritis patients with concomitant dry eye disease. We examined 40 rheumatoid arthritis patients with variable severity and 44 volunteer age- and gender-matched healthy control subjects. We found that all examined parameters were significantly lower (p < 0.05) in rheumatoid arthritis patients as opposed to the control samples: namely, the number of fibers, the total length of the nerves, the number of branch points on the main fibers and the total nerve-fiber area. We examined further variables, such as age, sex and the duration of rheumatoid arthritis. Interestingly, we could not find a correlation between the above variables and abnormal neural structural changes in the cornea. We interpreted these findings via implementing our hypotheses. Correspondingly, one neuroimmunological link between dry eye and rheumatoid arthritis could be through the chronic Piezo2 channelopathy-induced K2P-TASK1 signaling axis. This could accelerate neuroimmune-induced sensitization on the spinal level in this autoimmune disease, with Langerhans-cell activation in the cornea and theorized downregulated Piezo1 channels in these cells. Even more importantly, suggested principal primary-damage-associated corneal keratocyte activation could be accompanied by upregulation of Piezo1. Both activation processes on the periphery would skew the plasticity of the Th17/Treg ratio, resulting in Th17/Treg imbalance in dry eye, secondary to rheumatoid arthritis. Hence, chronic somatosensory-terminal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could result in a mixed picture of disrupted functional regeneration but upregulated morphological regeneration activity of these somatosensory axons in the cornea, providing the demonstrated abnormal neural corneal morphology.

Effect of liposomal formulation of ascorbic acid on corneal permeability.

Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues.

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window.

Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-ß-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.

The Assessment of Acute Chorioretinal Changes Due to Intensive Physical Exercise in Senior Elite Athletes.

Regular physical exercise is known to lower the incidence of age-related eye diseases. We aimed to assess the acute chorioretinal alterations in older adults following intense physical strain. Seventeen senior elite athletes were recruited who underwent an aerobic exercise on a cycle ergometer and macular scanning by optical coherence tomography. A significant thinning of the entire retina was observed 1 min after exercise, followed by a thickening at 5 min, after which the thickness returned to baseline. This trend was similar in almost every single retinal layer, although a significant change was observed only in the inner retina. Choroidal thickness changes were neither significant nor did they correlate with the thickness changes of intraretinal layers. The mechanism of how these immediate retinal changes chronically impact age-related sight-threatening pathologies that, in turn, result in a substantially reduced quality of life warrants further investigation on nontrained older adults as well.

[Congenital aniridia - Hungarian data of a spectrum disease]. / Congenitalis aniridia ­ egy spektrumbetegség magyarországi adatai.

INTRODUCTION: Congenital aniridia is a rare disease, characterised by the complete or partial absence of the iris, but lesions may be present in all structures of the eye. OBJECTIVE: To determine the prevalence of ocular diseases in congenital aniridia by analyzing patients from a Hungarian centre. PATIENTS AND METHODS: Patients at the Department of Ophthalmology of Semmelweis University, examined between October 2005 and May 2022, have been included. After taking the patients' medical history, a detailed ophthalmological examination has been performed. RESULTS: Of the 82 patients in the database, 33 (age 25.69 ± 17.49 [5-59] years, 17 females [51.51%]) presented for examination and 65 eyes were examined. Nystagmus was found in 45 eyes of 23 patients (69.23%), and the patients' uncorrected distance visual acuity was 0.14 ± 0.128 (0.9 logMAR; 0.63-0.005). The aniridia-associated keratopathy was Grade 0 in 8 eyes (12.3%), Grade 1 in 10 eyes (15.38%), Grade 2 in 16 eyes (24.62%), Grade 3 in 4 eyes (6.15%) and Grade 4 in 25 eyes (38.46%). 30 eyes (46.15%) of 15 patients had secondary glaucoma, 6 eyes (9.2%) of 3 patients were glaucoma suspect. 8 eyes (12.3%) had a clear lens, 44 eyes (67.69%) had cataract, of which 22 (33.84%) were anterior cortical polar cataracts. 13 eyes (20%) were pseudophakic (PCL) and 7 eyes (10.77%) had lens dislocation or zonular insufficiency. Macular hypoplasia was found in 6 eyes of 3 patients (4.6%) and optic nerve head malformation in 2 eyes of 1 patient (3.03%). CONCLUSION: The ocular signs of congenital aniridia are aniridia-associated keratopathy, secondary glaucoma, cataract, macular and optic nerve head hypoplasia. Systematic collaboration of different ophthalmological specialties is required for the management and care of all these ocular abnormalities. Orv Hetil. 2023; 164(4): 148-155.

Examination of corneal microstructure in the quiescent phase of vernal keratoconjunctivitis using in vivo confocal microscopy.

INTRODUCTION: This study investigated the morphological characteristics of corneal microstructure in the quiescent phase of vernal keratoconjunctivitis (VKC). METHODS: Twenty patients with quiescent VKC and 25 healthy subjects were included. In vivo confocal microscopy (IVCM) of the central cornea was performed. Cellular density of each layer and the morphology of subbasal nerve plexus (SBNP) was analysed. Langerhans cell density (LCD), morphology (LCM), and field area (LCF) were also examined. RESULTS: No differences were found either in cell densities nor in SBNP morphology (p > 0.05). LCD, LCM and LCF were significantly higher in the VKC group (p = 0.005, p < 0.001 and p < 0.001, respectively). The severity of papillary hypertrophy had a significant impact on LCD, LCM and LCF (ß-coefficient: 19.541, p < 0.001; ß-coefficient: 0.283, p < 0.001 and ß-coefficient: 595.255, p < 0.001, respectively). DISCUSSION: In quiescent VKC, LCD, LCM, and LCF were increased, and they were associated with the severity of papillary hypertrophy. Alterations of Langerhans cells indicate a subclinical inflammatory process without ocular symptoms.

Presence of SARS-CoV-2 on the conjunctival mucosa in patients hospitalized due to COVID-19: Pathophysiological considerations and therapeutic implications.

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa. Aim: To prove that SARS-CoV-2 can be detected in the conjunctiva. Methods: Previously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed. Results: The study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery. Conclusions: Although only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that - in addition to the respiratory tract - the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.

Erythromycin-loaded polymeric micelles: In situ gel development, in vitro and ex vivo ocular investigations.

Our present series of experiments was to create a value-added formulation that has the potential to exert a powerful and long-lasting antibacterial effect for use in ophthalmology. Erythromycin-loaded polymeric micelles were formulated with a micelle size of 87.14 nm in a monodisperse distribution with 86.94 % encapsulation efficiency. To decrease the polymeric micelle-like burst effect of these nanoparticles, the formulation was dispersed in a Carbopol 934P gel base to prolong the drug release and permeation profile of erythromycin. With successful incorporation, a short gelling time with proper sol to gel transition was experienced in the form of transparent gels. The optimized formulation has high mucoadhesion which is a critical factor for prolonging residence time. With the initial burst, the drug release was saturated with more than 75 % of the drug released in simulated tear fluid. Corneal permeability investigations revealed that the gel formulation provides the value-added properties of polymeric micelles, with elevated permeability through into the aqueous humour across the cornea. While retaining its antimicrobial activity, the formulation may be capable to be utilized as an innovative ophthalmic formulation for treating bacterial infections of the eye.

The assessment of acute chorioretinal changes due to intensive physical exercise in young adults.

PURPOSE: There is abundant evidence on the benefits of physical activity on cardiovascular health. However, there are only few data on the acute effects of physical exercise on the retina and choroid. Our aim was the in vivo examination of chorioretinal alterations following short intense physical activity by spectral domain optical coherence tomography (SD-OCT). METHODS: Twenty-one eyes of 21 healthy, young subjects (mean age 22.5 ± 4.1 years, 15 males and 6 females) were recruited. Macular scanning with a SD-OCT was performed before and following a vita maxima-type physical strain exercise on a rowing ergometer until complete fatigue. Follow-up OCT scans were performed 1, 5, 15, 30 and 60 minutes following the exercise. The OCT images were exported and analyzed using our custom-built OCTRIMA 3D software and the thickness of 7 retinal layers was calculated, along with semi-automated measurement of the choroidal thickness. One-way ANOVA analysis was performed followed by Dunnett post hoc test for the thickness change compared to baseline and the correlation between performance and thickness change has also been calculated. The level of significance was set at 0.001. RESULTS: We observed a significant thinning of the total retina 1 minute post-exercise (-7.3 ± 0.6 µm, p < 0.001) which was followed by a significant thickening by 5 and 15 minutes (+3.6 ± 0.6 µm and +4.0 ± 0.6 µm, respectively, both p <0.001). Post-exercise retinal thickness returned to baseline by 30 minutes. This trend was present throughout the most layers of the retina, with significant changes in the ganglion cell-inner plexiform layer complex, (-1.3 ± 0.1 µm, +0.6 ± 0.1 µm and +0.7 ± 0.1 µm, respectively, p <0.001 for all), in the inner nuclear layer at 1 and 5 minutes (-0.8 ± 0.1 µm and +0.8 ± 0.1 µm, respectively, p <0.001 for both), in the outer nuclear layer-photoreceptor inner segment complex at 5 minute (+2.3 ± 0.4 µm, p <0.001 for all) and in the interdigitation zone-retinal pigment epithelium complex at 1 and 15 minutes (-3.3 ± 0.4 µm and +1.8 ± 0.4 µm, respectively, p <0.001 for both). There was no significant change in choroidal thickness; however, we could detect a tendency towards thinning at 1, 15, and 30 minutes following exercise. The observed changes in thickness change did not correlate with performance. Similar trends were observed in both professional and amateur sportsmen (n = 15 and n = 6, respectively). The absolute changes in choroidal thickness did not show any correlation with the thickness changes of the intraretinal layers. CONCLUSIONS: Our study implies that in young adults, intense physical exercise has an acute effect on the granular layers of the retina, resulting in thinning followed by rebound thickening before normalization. We could not identify any clear correlation with either choroidal changes or performance that might explain our observations, and hence the exact mechanism warrants further clarification. We believe that a combination of vascular and mechanic changes is behind the observed trends.

Ocular treatment of cystinosis with eye drop containing cysteamine / Ciszteamintartalmú szemcsepp alkalmazása cystinosisban

Cystinosis is a rare lysosomal storage disease affecting amino acid metabolism, characterized by the accumulation and crystallization of cystine in various tissues, primarily in the eye and kidney. The major ophthalmic symptom is photophobia, which is related to the corneal deposition of cystine crystals. The light sensitivity significantly impairs the quality of life of the affected patients, thus, effective ophthalmic treatment to reduce the crystal density is very importance. In the current case report, we present the characteristic ocular clinical appearance and treatment options of cystinosis by reviewing the literature. A simple aqueous solution of cysteamine, which aids in the dissolution of crystals, has been widely used in topical treatment in the past, however, its therapeutic efficacy is debatable. Recently, a new viscous formulation of cysteamine has been proposed for ophthalmic treatment. For the treatment of corneal cystine crystals in our patient, the new viscous format of cysteamine has been applied, and therapeutic effects were recorded for a year. Applying the viscous cysteamine formulation, a marked and gradual decrease in photophobia was observed in our patient in the first year of the treatment. Anterior-segment optical coherence tomography and in vivo confocal microscopy represented a continuous decrease in the density of corneal crystals even from the first month of the treatment period. The aim of our case report is to present the ophthalmic symptoms of cystinosis and the results of the first clinical application of viscous formulation of cysteamin eye drops in Hungary in a cystinosis patient.

Corneal Densitometry and In Vivo Confocal Microscopy in Patients with Monoclonal Gammopathy-Analysis of 130 Eyes of 65 Subjects.

BACKGROUND: Corneal imaging may support an early diagnosis of monoclonal gammopathy. The goal of our study was to analyze corneal stromal properties using Pentacam and in vivo confocal cornea microscopy (IVCM) in subjects with monoclonal gammopathy. PATIENTS AND METHODS: In our cross-sectional study, patients with monoclonal gammopathy (130 eyes of 65 patients (40.0% males; age 67.65 ± 9.74 years)) and randomly selected individuals of the same age group, without hematological disease (100 eyes of 50 control subjects (40.0% males; age 60.67 ± 15.06 years)) were included. Using Pentacam (Pentacam HR; Oculus GmbH, Wetzlar, Germany), corneal stromal light scattering values were obtained (1) centrally 0-2 mm zone; (2) 2-6 mm zone; (3) 6-10 mm zone; (4) 10-12 mm zone. Using IVCM with Heidelberg Retina Tomograph with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany), the density of hyperreflective keratocytes and the number of hyperreflective spikes per image were manually analyzed, in the stroma. RESULTS: In the first, second and third annular zone, light scattering was significantly higher in subjects with monoclonal gammopathy, than in controls (p ≤ 0.04). The number of hyperreflective keratocytes and hyperreflective spikes per image was significantly higher in stroma of subjects with monoclonal gammopathy (p ≤ 0.012). CONCLUSIONS: Our study confirms that increased corneal light scattering in the central 10 mm annular zone and increased keratocyte hyperreflectivity may give rise to suspicion of monoclonal gammopathy. As corneal light scattering is not increased at the limbal 10-12 mm annular zone in monoclonal gammopathy subjects, our spatial analysis provides evidence against the limbal origin of corneal paraprotein deposition. Using IVCM, stromal hyperreflective spikes may represent specific signs of monoclonal gammopathy.

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.

Factors influencing haze formation and corneal flattening, and the impact of haze on visual acuity after conventional collagen cross-linking: a 12-month retrospective study.

BACKGROUND: Our aim was to determine associations of pachymetry, keratometry, and their changes with haze formation and corneal flattening after collagen cross-linking, and to analyse the relationship between postoperative haze and visual outcome. METHODS: Retrospective analysis was performed on 47 eyes of 47 patients with keratoconus using the Pentacam HR Scheimpflug camera before and 1, 3, 6 and 12 months after cross-linking. Corneal backscattered light values in grey scale unit were recorded in the anterior, center and posterior corneal layers and in four concentric rings. Surface area- and thickness-corrected grey scale unit values were assessed with an additional calculation. Friedman test with post hoc Wilcoxon signed-rank test was used to analyse changes in visual acuity, pachymetry, keratometry and densitometry. Spearman's rank correlation test was used to detect correlations of haze formation and corneal flattening with pachymetry, keratometry and their postoperative change. Generalized estimating equations analysis was used to investigate the influence of densitometry values on postoperative visual acuity after controlling for the effect of preoperative keratometry. RESULTS: One year after treatment, significant flattening was observed in maximum and mean keratometry readings (p < 0.001). Significantly increased densitometry values were observed in three central rings compared to baseline (post hoc p < 0.0125). According to receiver operating characteristic curve, densitometry value of the anterior layer of 0-2 mm ring was the most characteristic parameter of densitometry changes after cross-linking (area under the curve = 0.936). Changes in haze significantly correlated with preoperative maximum keratometry (R = 0.303, p = 0.038) and with the changes in maximum keratometry (R = -0.412, p = 0.004). Changes in maximum keratometry correlated with preoperative maximum keratometry (R = -0.302, p = 0.038). Postoperative haze had a significant impact on uncorrected and best corrected distance visual acuity (ß coefficient = 0.006, p = 0.041 and ß coefficient = 0.003, p = 0.039, respectively). CONCLUSIONS: Our findings indicate that in more advanced keratoconus more significant corneal flattening effect parallel with haze formation can be observed after cross-linking. Despite significant reduction of keratometry, postoperative corneal haze may limit final visual acuity.