Retinal Microcirculation Measurements in Response to Endurance Exercises Analysed by Adaptive Optics Retinal Camera.

This study aimed to precisely investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers through adaptive optics retinal camera (AO) measurement. We included healthy volunteers (11 men and 14 women) aged 20.6 ± 0.9. The heart rate (HR) and systolic and diastolic blood pressures (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the AO-rtx1TM (Imagine Eyes, Orsay, France) without pupil dilation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Cardiovascular parameter results: After exercise, SBP, DBP, and HR changed significantly from 130.2 ± 13.2 to 159.7 ± 15.6 mm Hg, 81.2 ± 6.3 to 77.1 ± 8.2 mm Hg, and 80.8 ± 16.1 to 175.0 ± 6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis showed no significant decrease in LD, Wall 1 after exercise: from 96.0 ± 6.8 to 94.9 ± 6.7 (p = 0.258), from 11.0 ± 1.5 to 10.4 ± 1.5 (p = 0.107), respectively, and significant reduction in VD from 118.5 ± 8.3 to 115.9 ± 8.3 (p = 0.047), Wall 2 from 11.5 ± 1.0 to 10.7 ± 1.3 (p = 0.017), WLR from 0.234 ± 0.02 to 0.222 ± 0.010 (p = 0.046), WCSA from 3802.8 ± 577.6 to 3512.3 ± 535.3 (p = 0.016). The AO is a promising technique for investigating the effects of exercise on microcirculation, allowing for the tracking of changes throughout the observation. Intensive dynamic physical exertion increases blood pressure and heart rate and causes the vasoconstriction of small retinal arterioles due to the autoregulation mechanism.

Malignant Hypertension:A Systemic Cardiovascular Disease: JACC Review Topic of the Week.

Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.

Is Primary Open-Angle Glaucoma a Vascular Disease? Assessment of the Relationship between Retinal Arteriolar Morphology and Glaucoma Severity Using Adaptive Optics.

BACKGROUND: Retinal vascular abnormalities may be associated with glaucomatous damage. Adaptive optics (AO) is a new technology that enables the analysis of retinal vasculature at the cellular level in vivo. The purpose of this study was to evaluate retinal arteriolar parameters using the rtx1 adaptive optics fundus camera (AO-FC) in patients with primary open-angle glaucoma (POAG) at different stages and to investigate the relationship between these parameters and changes in spectral-domain optical coherence tomography (SD-OCT) and perimetry. METHODS: Parameters of the retinal supratemporal and infratemporal arterioles (wall thickness (WT), lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and cross-sectional area of the vascular wall (WCSA)) were analysed with the rtx1 in 111 POAG eyes, which were divided into three groups according to the severity of the disease, and 70 healthy eyes. The associations between RTX1 values and the cup-to-disk ratio, SD-OCT parameters, and visual field parameters were assessed. RESULTS: Compared with the control group, the POAG groups showed significantly smaller TD and LD values (p < 0.05) and significantly higher WLR and WT values (p < 0.05) for the supratemporal and infratemporal arterioles. TD was significantly positively correlated with the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) (p < 0.05). LD was significantly positively correlated with the RNFL, GCC, and rim area (p < 0.05). The WLR was significantly negatively correlated with the RNFL, GCC, rim area, and MD (p < 0.05), while it was significantly positively correlated with the cup-to-disc ratio and PSD (p < 0.05). CONCLUSIONS: The results suggest that vascular dysfunction is present in POAG, even at a very early stage of glaucoma, and increases with the severity of the disease.

Clinical Application of Adaptive Optics Imaging in Diagnosis, Management, and Monitoring of Ophthalmological Diseases: A Narrative Review.

Visualization of the retinal structure is crucial for understanding the pathophysiology of ophthalmic diseases, as well as for monitoring their course and treatment effects. Until recently, evaluation of the retina at the cellular level was only possible using histological methods, because the available retinal imaging technology had insufficient resolution due to aberrations caused by the optics of the eye. Adaptive optics (AO) technology improved the resolution of optical systems to 2 µm by correcting optical wave-front aberrations, thereby revolutionizing methods for studying eye structures in vivo. Within 25 years of its first application in ophthalmology, AO has been integrated into almost all existing retinal imaging devices, such as the fundus camera (FC), scanning laser ophthalmoscopy (SLO), and optical coherence tomography (OCT). Numerous studies have evaluated individual retinal structures, such as photoreceptors, blood vessels, nerve fibers, ganglion cells, lamina cribrosa, and trabeculum. AO technology has been applied in imaging structures in healthy eyes and in various ocular diseases. This article aims to review the roles of AO imaging in the diagnosis, management, and monitoring of age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, hypertensive retinopathy (HR), central serous chorioretinopathy (CSCR), and inherited retinal diseases (IRDs).

The immunology of corneal limbal stem cells: the up-to-date approach to stem cell transplantation.

Limbal epithelial stem cells (LSC, LESC) are multipotent cells used as regenerative treatment of the cornea in patients with limbal epithelial stem cell deficiency (LSCD, LESCD). There are different types of stem cell grafting including cultivated limbal epithelial transplantation (CET) and simple limbal epithelial transplantation (SLET). The outcomes of the techniques have been assessed as similar, with differences in the sample size required during the procedures. The most important culture components for stem cell cultivation include 3T3 murine fibroblasts, human amniotic membrane (HAM), fibrin gel, and culture medium. The culture medium may be enriched with serum or not; however, xenobiotic-free materials are preferred because of the low risk of pathogen transmission. Multiple studies have defined molecules important for maintaining the function of LSC including C/EBP δ, Bmi-1, p63 α, interleukins (IL-6), epithelial structural proteins - keratins, and antibodies against epidermal growth factor receptor (EGFR). The cell phenotype of LSC has been described with factors of transplantation success rate such as a high percentage of p63 positive cells. The article emphasizes the role of recipient tissue preparation, modern cultivation techniques and pathophysiological processes in LSC transplantation effectiveness.

Progression of Rare Inherited Retinal Dystrophies May Be Monitored by Adaptive Optics Imaging.

Inherited retinal dystrophies (IRDs) are bilateral genetic conditions of the retina, leading to irreversible vision loss. This study included 55 eyes afflicted with IRDs affecting the macula. The diseases examined encompassed Stargardt disease (STGD), cone dystrophy (CD), and cone-rod dystrophy (CRD) using adaptive optics (Rtx1™; Imagine Eyes, Orsay, France). Adaptive optics facilitate high-quality visualisation of retinal microstructures, including cones. Cone parameters, such as cone density (DM), cone spacing (SM), and regularity (REG), were analysed. The best corrected visual acuity (BCVA) was assessed as well. Examinations were performed twice over a 6-year observation period. A significant change was observed in DM (1282.73/mm2 vs. 10,073.42/mm2, p< 0.001) and SM (9.83 µm vs. 12.16 µm, p< 0.001) during the follow-up. BCVA deterioration was also significant (0.16 vs. 0.12, p = 0.001), albeit uncorrelated with the change in cone parameters. No significant difference in REG was detected between the initial examination and the follow-up (p = 0.089).

Characteristics of Rare Inherited Retinal Dystrophies in Adaptive Optics-A Study on 53 Eyes.

Inherited retinal dystrophies (IRDs) are genetic disorders that lead to the bilateral degeneration of the retina, causing irreversible vision loss. These conditions often manifest during the first and second decades of life, and their primary symptoms can be non-specific. Diagnostic processes encompass assessments of best-corrected visual acuity, fundoscopy, optical coherence tomography, fundus autofluorescence, fluorescein angiography, electrophysiological tests, and genetic testing. This study focuses on the application of adaptive optics (AO), a non-invasive retinal examination, for the assessment of patients with IRDs. AO facilitates the high-quality, detailed observation of retinal photoreceptor structures (cones and rods) and enables the quantitative analysis of parameters such as cone density (DM), cone spacing (SM), cone regularity (REG), and Voronoi analysis (N%6). AO examinations were conducted on eyes diagnosed with Stargardt disease (STGD, N=36), cone dystrophy (CD, N=9), and cone-rod dystrophy (CRD, N=8), and on healthy eyes (N=14). There were significant differences in the DM, SM, REG, and N%6 parameters between the healthy and IRD-affected eyes (p<0.001 for DM, SM, and REG; p=0.008 for N%6). The mean DM in the CD, CRD, and STGD groups was 8900.39/mm2, 9296.32/mm2, and 16,209.66/mm2, respectively, with a significant inter-group difference (p=0.006). The mean SM in the CD, CRD, and STGD groups was 12.37 µm, 14.82 µm, and 9.65 µm, respectively, with a significant difference observed between groups (p=0.002). However, no significant difference was found in REG and N%6 among the CD, CRD, and STGD groups. Significant differences were found in SM and DM between CD and STGD (p=0.014 for SM; p=0.003 for DM) and between CRD and STGD (p=0.027 for SM; p=0.003 for DM). Our findings suggest that AO holds significant potential as an impactful diagnostic tool for IRDs.

Retinal Photoreceptors and Microvascular Changes in the Assessment of Diabetic Retinopathy Progression: A Two-Year Follow-Up Study.

BACKGROUND: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, Orsay, France) is a retinal camera that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. OBJECTIVE: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two follow-up appointments, one and two years after the study, beginning with Rtx1TM image acquisition, visual acuity assessment, macular OCT scans and blood measurements. RESULTS: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements showed decreased photoreceptor and microvascular parameters in the DR group compared with the control group. Furthermore, in the 2-year follow-up, both groups' Rtx1TM-acquired morphological changes were statistically significant. CONCLUSIONS: Rtx1TM technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.

Impact of Arterial Hypertension on the Eye: A Review of the Pathogenesis, Diagnostic Methods, and Treatment of Hypertensive Retinopathy.

The number of patients with arterial hypertension is continually increasing. Hypertension can cause organ complications, called hypertension-mediated organ damage (HMOD). One example is hypertensive retinopathy, in which high blood pressure (BP) damages both the retinal microcirculation and the retinal nerve fiber layer (RNFL). This can result in progressive and painless vision deterioration in some groups of patients. Unlike anywhere else in the human body, the microvasculature of the retina can be observed in vivo, and the progression of changes can be closely monitored. The harmful effect of increased BP on the eye is not only limited to hypertensive retinopathy, but can also lead to an exacerbation of diabetic retinopathy (DR) and to an increase in intraocular pressure (IOP), and it can also trigger the formation of thromboembolic lesions. This review presents an update on the pathogenesis of hypertensive retinopathy and the use of adaptive optics (AO) combined with optical coherence tomography (OCT) to evaluate the retinal microvasculature. The latest progress and directions of research in the field of hypertensive retinopathy are also discussed.

Immunological and molecular basics of the primary open angle glaucoma pathomechanism.

Glaucoma is a degenerative process of the optic nerve. Increased intraocular pressure is believed to be the main factor leading to the glaucomatous damage. The in vitro and in vivo animal glaucoma research models provide insight into the molecular changes in the retina in response to the injury factor. The damage is a complex process incorporating molecular and immunological changes. Such changes involve NF kB activity and complement activation. The processes affect the human antigen, JNK, MAPK, p53, MT2 and DBA/2J molecular pathways, activate the autophagy processes and compromise neuroprotective mechanisms. Activation and inhibition of immunological responses contribute to cell injury. The immunological mechanisms of glaucomatous degeneration include glial response, the complement, tumor necrosis factor α (TNF-α) pathways and toll-like receptors athways. Oxidative stress and excitotoxicity are factors contributing to cell death in glaucoma. The authors present an up-to-date review of the mechanisms involved and update on research focusing on a possible innovative glaucoma treatment.

The Relation between Body Mass Index and Retinal Photoreceptor Morphology and Microvascular Changes Measured with Adaptive Optics (rtx1) High-Resolution Imaging.

BACKGROUND: Overweight and obese patients are at risk for diabetes, cardiovascular disorders, and microvascular complications. The rtx1TM (Imagine Eyes, France) is a microscope that allows near histological visualizations of cones and retinal microcirculation. OBJECTIVE: This study analysed the cones and retinal microvascular changes in a group of 47 healthy women with different BMI values. Participants were divided into 2 groups: the BMI group (28 women with BMI >/25) and the control group (19 lean women with BMI <25). RESULTS: The lumen and diameter of retinal arteries were not significantly different between groups. There were significant differences in the thickness of arteriole walls. The WLR and WCSA values differed significantly between the control and BMI groups (for WLR 0.25 ± 0.03 vs. 0.29 ± 0.03, p < 0.001; for WCSA 4136.7 ± 1140.0 vs. 5217.3 ± 944.0, respectively, p < 0.001). In healthy eyes, cone density and morphology were not affected by weight. CONCLUSIONS: Retinal image analysis with rtx1 offers a novel noninvasive measurement of early changes in retinal vasculature that are not detectable during routine clinical examination. Abnormalities of retinal arterioles found by rtx1™examination should be considered as a strong risk factor for cardiovascular changes resulting from overweight and obesity.

Extracellular MMP-9-Based Assessment of Ocular Surface Inflammation in Patients with Primary Open-Angle Glaucoma.

PURPOSE: Objective assessment of dry eye disease (DED) severity and ocular inflammation using the InflammaDry® test for extracellular matrix metalloproteinase-9 (MMP-9) and the impact of antiglaucoma eye drops in people with primary open-angle glaucoma (POAG). METHODS: Overall, 90 adults (180 eyes) were included: 60 had been diagnosed with POAG and were treated with prostaglandin analogue monotherapy and 30 were suspected of having POAG but did not receive any treatment (control group). Of those treated with prostaglandin eye drops, 30 received a preservative-free formulation (tafluprost) and 30 were treated with a formulation containing the preservative benzalkonium chloride (BAK) (latanoprost). Measurement of extracellular MMP-9 levels (InflammaDry test) provided a marker for ocular surface inflammation. Further assessments of disease severity and inflammation comprised Goldmann applanation tonometry for intraocular pressure (IOP), Schirmer's test with anesthesia, ocular surface staining with unpreserved fluorescein (Oxford scale index), tear breakup time (TBUT), McMonnies questionnaire, and the Ocular Surface Disease index (OSDI). RESULTS: Clinically significant MMP-9 levels (>40 ng/mL) were detected in tear film from 46.7% of subjects treated with BAK-containing medication. In contrast, only 16.7% of subjects treated with preservative-free medication or untreated individuals demonstrated similar MMP-9 levels. This difference was statistically significant (p < 0.05). MMP-9 results correlated with other indicators of inflammation and disease severity. BAK-containing medication was associated with rapid TBUT (<5 seconds) in 50% of cases, while only 10% of untreated subjects and individuals using preservative-free medication demonstrated comparable TBUT results. CONCLUSION: Measurement of ocular surface MMP-9 level provides a useful marker for inflammation and DED in POAG. Use of a preservative-free topical prostaglandin formulation results in lower levels of ocular inflammation, compared with BAK-containing medication.

Adaptive Optics (rtx1) High-Resolution Imaging of Photoreceptors and Retinal Arteries in Patients with Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of impaired vision in patients with diabetes mellitus. An adaptive optics retinal camera (rtx1™; Imagine Eyes, France) was used to capture images of cones and retinal arteries from patients with DR. OBJECTIVE: Cone parameters (density, interphotoreceptor distance, and regularity) and retinal artery parameters (wall thickness, lumen diameter, WLR, and WCSA) were analyzed in 36 patients with nonproliferative DR (NPDR; 22 with mild NPDR and 14 with moderate NPDR) and in 20 healthy volunteers (the control group). RESULTS: Cone density at 2° eccentricities was significantly lower in the DR compared to the control group (19822 ± 4342 cells/mm2 vs. 24722 ± 3507 cells/mm2, respectively). Cone density and regularity decreased with increasing severity of DR. The artery walls were significantly thicker in the DR group. The WLR and WCSA differed significantly between the DR and the control groups (WLR 0.339 ± 0.06 vs. 0.254 ± 0.04; WCSA 5567 ± 1140 vs. 4178 ± 944, respectively). CONCLUSIONS: Decreased cone regularity and density are seen in patients with mild and moderate NPDR. Abnormalities of retinal arterioles show signs of arteriolar dysfunction in DR. Retinal image analysis with the rtx1 offers a novel noninvasive measurement of early changes in the neural cells and retina vasculature in diabetic eyes.

The RELIEF study: Tolerability and efficacy of preservative-free latanoprost in the treatment of glaucoma or ocular hypertension.

PURPOSE:: To assess tolerability and efficacy following a switch from benzalkonium chloride-latanoprost to preservative-free latanoprost in patients with glaucoma or ocular hypertension. METHODS:: A total of 140 patients with glaucoma or ocular hypertension controlled with benzalkonium chloride-latanoprost for at least 3 months were switched to treatment with preservative-free latanoprost. Assessments were made on days 15, 45, and 90 (D15, D45, and D90) and included best-corrected visual acuity, intraocular pressure, slit lamp examination, fluorescein staining, tear film break-up time, patient symptom evaluation, and subjective estimation of tolerability. RESULTS:: Mean best-corrected visual acuity remained unchanged during the study. Mean intraocular pressure compared with baseline (D0) remained stable throughout the study (D0, 15.9 mmHg (standard deviation = 2.6); D90, 15.3 mmHg (standard deviation = 2.4); p < 0.006). Tear film break-up time improved or remained unchanged relative to baseline in 92% of patients at D45 and in 93% at D90. Moderate-to-severe conjunctival hyperemia was seen in 56.8% of patients at D0, but this figure decreased to 13.7%, 2.2%, and 1.6% at D15, D45, and D90, respectively. Subjective assessment of tolerability (0-10 scale) indicated improvement with change of therapy (mean score: 5.3 (standard deviation = 2.2) at D0 versus 1.9 (standard deviation = 1.7) at D90; p < 0.0001). CONCLUSION:: Preservative-free latanoprost has at least the same intraocular pressure-lowering efficacy as benzalkonium chloride-latanoprost, with a better tolerability profile. This may translate into greater control of treatment and improved quality of life.

Analysis of the polymorphic variants of RAN and GEMIN3 genes and risk of Primary Open-Angle Glaucoma in the Polish population.

BACKGROUND: Glaucoma is considered as a neurodegenerative disorder in which the optic nerve damage leads to irreversible blindness. Many scientific findings indicate miRNA implication in the neurodegeneration process. In this study, we aimed to evaluate the polymorphic variants of miRNA processing genes, RAN (rs14035) and GEMIN3 (rs197388), and their association with a risk of primary open-angle glaucoma (POAG) in relation to selected clinical parameters. MATERIALS AND METHODS: The study included 246 POAG patients and 188 controls. The selected gene polymorphisms were analyzed by TaqMan SNP Genotyping Assay using DNA extracted from blood samples. RESULTS: The obtained results indicated that the AA genotype of rs197388 as well as the A allele in the same gene may be associated with an elevated risk of POAG development (P = 0.021, P = 0.017 respectively). The correlation between the data and clinical parameters has shown that the A allele of rs197388 in relation to retinal nerve fiber layer(RNFL) could be responsible for an increased risk of glaucoma occurrence (P = 0.028), while the AT genotype could be associated with a decreased risk of POAG according to the mean deviation parameter (P = 0.023). CONCLUSION: Our data has shown that GEMIN3 gene (rs197388) polymorphisms might be associated with a risk of POAG development in the Polish population. This is the first report evaluating the polymorphic variants of miRNA processing genes, RAN and GEMIN3, with a changed risk of glaucoma.

Retinal Photoreceptors and Microvascular Changes in Prediabetes Measured with Adaptive Optics (rtx1™): A Case-Control Study.

BACKGROUND: Patients with prediabetes are at risk for diabetes, cardiovascular events, and microvascular complications. The rtx1 (Imagine Eyes, France) permits early detection of changes in the retinal photoreceptors and vessels. OBJECTIVE: Cone parameters and retinal microvasculature were analyzed with the rtx1 in 12 prediabetic patients and 22 healthy subjects. The analysis was based on cone density (DM), interphotoreceptor distance (SM), cone packing regularity, and retinal vessel parameters: wall thickness, lumen diameter (LD), wall-to-lumen ratio (WLR), and cross-sectional area of the vascular wall. RESULTS: DM in the prediabetic group was not significantly lower than that in the control group (18,935 ± 1713 cells/mm2 and 19,900 ± 2375 cells/mm2, respectively; p = 0.0928). The LD and WLR means differed significantly between the prediabetic and the control groups (LD 94.3 ± 10.9 versus 101.2 ± 15, p = 0.022; WLR 0.29 ± 0.05 versus 0.22 ± 0.03, p < 0.05). A multivariate regression analysis showed that the WLR was significantly correlated with BMI and total cholesterol. CONCLUSIONS: Abnormalities found in rtx1 examinations indicated early signs of arteriolar dysfunction, prior to impaired glucose tolerance progressing to diabetes. The rtx1 retinal image analysis offers noninvasive measurement of early changes in the vasculature that routine clinical examination cannot detect.

Is atrial fibrillation a risk factor for normal-tension glaucoma?

Glaucoma (GL) and atrial fibrillation (AF) are diseases of significant social importance. Cardiovascular disorders such as systemic hypertension, hypotension, increased blood viscosity, vasospasm, and diabetes are potential risk factors of GL, especially when intraocular pressure is not elevated. Only a few studies have reported a possible connection between cardiac arrhythmias and GL. The purpose of this study was to evaluate the risk of GL in patients with AF.A total of 117 patients were included in the study, 79 with AF (AF group) and 38 with sinus rhythm (Control group), matched for age and sex. The mean ±â€Šstandard deviation age was 73.6 ±â€Š7.2 and 71.6 ±â€Š4.7 years for the AF and control groups, respectively. There were no statistically significant differences in the percentage of systemic hypertension, congestive heart failure, diabetes mellitus type 2, or vascular disease between the groups. Patients were examined for the presence of normal-tension glaucoma (NTG) by an ophthalmologist.NTG was confirmed in 40 patients (34.2%) in the entire group, with 35 (44.3%) in the AF group and 5 (13.15%) in the Control group. The incidence of NTG was significantly higher in the AF group (P = .0221). Women represented 60% of GL patients in the AF group and 80% in the control group. There were no significant differences in intraocular pressure between the groups (mean ±â€Šstandard deviation, 14.3 ±â€Š2.3 vs. 14.2 ±â€Š2.8 mmHg, P = .4202). Approximately three-fourths of patients with AF and NTG had early visual field damage based on the Hodapp classification.AF, independent of other known cardiovascular risk factors, increases the risk of developing NTG. Many AF patients do not have conspicuous symptoms of GL, so understanding the possible risk of its development is critical because early detection might help to prevent later visual impairment and even irreversible blindness.

Human photoreceptor cone density measured with adaptive optics technology (rtx1 device) in healthy eyes: Standardization of measurements.

The anatomic structures of the anterior segment of the eye enable correct reception of stimuli by the retina, which contains receptors that receive light impulses and transmit them to the visual cortex. The aim of this study was to assess the effect of the size of the sampling window in an adaptive optics (AO) flood-illumination retinal camera (rtx1) on cone density measurements in the eyes of healthy individuals and to investigate the differences in cone density and spacing in different quadrants of the retina. Thirty-three subjects with no ophthalmic or systemic disease underwent a detailed ophthalmologic examination. Photographs of retinal fragments 3 degrees from the fovea were taken using the rtx1 AO retinal camera. We used sampling windows with 3 sizes (50 × 50, 100 × 100, and 250 × 250 µm). Cone density, spacing, and shape were determined using AOdetect software. The median (interquartile range) cone density was 19,269 (4964) cones/mm. There were statistically significant differences between measurements taken with the 50/50 and 250/250-m windows. There were no significant differences in the cone spacing results between any of the windows examined, but the measurements differed according to location between the superior and temporal quadrants. The most common cone shape was hexagonal (47.6%) for all window sizes and locations. These findings may help in the development of a normative database for variation in cone density in healthy subjects and to allow the best window to be chosen for obtain the most correct values for eccentricity measurements of 3 degrees. In our study, the optimal sampling window was 100 × 100 µm.

Electrophysiological testing as a method of cone-rod and cone dystrophy diagnoses and prediction of disease progression.

PURPOSE: To determine the characteristics of patients with cone (CD) and cone-rod dystrophies (CRD) and to evaluate the changes in flash electroretinograms in both groups. METHODS: The retrospective study involved 48 patients-34 with CRD and 14 with CD. The patients underwent full ophthalmological examination, including Goldmann perimetry and full-field flash electroretinogram (FERG) within the initial examination. These examinations were then repeated seven, or more, years later. The longest follow-up period was 10 years, with the mean at 8.2 years. During both examinations, we assessed the amplitudes of the b wave in the scotopic ERG test 0.01 (which reflects rod response), the maximal scotopic ERG test 3.0 (which reflects cone and rod response) and the photopic 3.0 ERG test (which reflects cone response). The results were then compared against normal values. RESULTS: The progression over time of ERG b wave amplitudes in the scotopic ERG 0.01, maximal scotopic ERG 3.0 and photopic ERG tests was assessed. There were significant differences in rod, maximal and cone responses, between CD and CRD patients. While rod responses were markedly decreased in CRD patients during their initial examination, the decrease in the rod function in both CD and CRD patients was similar in their follow-up examination (p = 0.2398). Moreover, during initial examination, maximal responses were less common amongst CRD patients, over those with CD. Following the observation period, patients suffering from CRD exhibited a significant decrease in both maximal (p = 0.0125) and cone (p = 0.0046) responses. CONCLUSION: The clinical course of CRD and CD may vary; however, the latter appears to have a more favourable course than former. Although, at initial examination, the cone function was more diminished in CD patients, the final examinations reveal a more significant drop for CRD patients. Consequently, a differential diagnosis is essential for treating patients and forecasting their disease progression.

Reactive oxygen species promote localized DNA damage in glaucoma-iris tissues of elderly patients vulnerable to diabetic injury.

Glaucoma is typically an insidious-onset disease with serious visual consequences that has been positively linked to diabetes mellitus (DM). Glaucoma is more often present in the elderly. Important prognostic factors of glaucoma may be oxidative stress resulting from the toxic effects of glucose, and diabetes-associated vascular complications. Fifty-five patients and control subjects aged 71.0+/-10.1 yrs were enrolled in this study. Iris-tissue samples from DM type-2 patients, primary open-angle glaucoma-positive and -negative DM patients, and from healthy subjects were examined by use of the alkaline comet assay. We measured the DNA damage as numbers of strand breaks (SBs), oxidized purines as glycosyl-formamido-glycosylase (Fpg)-susceptible sites, and oxidized pyrimidines as endonuclease III (Nth)-susceptible sites. It was found that the level of oxidative damage in iris tissue was statistically higher in DM and glaucoma patients than that in healthy controls (oxidized purines: 38.0% and 34.7% vs 15.4%; oxidized pyrimidines: 43.3% and 39.0% vs 23.3%; P<0.001). Interestingly, we found strongly elevated levels of oxidized purines and pyrimidines in glaucomatous patients who also had DM, in comparison with healthy controls (oxidized purines: 55.7% vs 15.4%; oxidized pyrimidines: 61.8% vs 23.3%; P<0.001). Our observations suggest that the generation of reactive oxygen species may promote localized DNA damage in glaucoma-iris tissues of elderly patients vulnerable to diabetic injury.