Development of Analytical Method for the Quantitation of Monoclonal Antibodies Solutions via Raman Spectroscopy: The Case of Bevacizumab.

Personalized dosages of monoclonal antibodies are being used more regularly to treat various diseases, rendering their quantitation more essential than ever for the right dose administration to the patients. A promising alternative, which overcomes the obstacles of the well-established chromatographic techniques regarding the quantification of biopharmaceuticals, is Raman spectroscopy. This study aimed to develop and validate a novel analytical method for the quantitation of bevacizumab in solutions via Raman spectroscopy. For this purpose, a droplet of the solution was left to dry on a highly reflective carrier and a home-made apparatus was employed for rotation of the sample. Hence, each recorded Raman spectrum was the average of the signal acquired simultaneously from multiple points on a circular circumference. The method was validated, and the detection limit of the antibody was found to be 1.06 mg/mL. Bevacizumab was found to be highly distributed at the formed coffee ring of the dried droplet, though this was a function of solution concentration. Finally, Raman spectra at different distances on the coffee ring were obtained from the four quarters. The lowest bevacizumab detection limit was found at a distance of 75 µm from the external side of the coffee ring and it was determined to be equal to 0.53 mg/mL.

Impact of Cataract Surgery on IOP and Ocular Structures in Normotensive Patients and Primary and Exfoliation Open-Angle Glaucoma Patients.

Purpose: The aim of this study was to evaluate and compare the changes in Intraocular Pressure (IOP) and other ocular parameters: the Anterior Chamber Angle (ACA), Anterior Chamber Volume (ACV), and Anterior Chamber Depth (ACD) during phacoemulsification surgery in Greek patients with normotensive eyes and those with well-controlled Open-Angle Glaucoma (OAG). Additionally, parameters such as the Corneal Thickness (CCT), Axial Length (AL), Central Macular Thickness (CMT), and Retinal Nerve Fibre Layer (RNFL) were also examined. Patients and Methods: This was a prospective observational case-control study that included 50 phakic eyes, 25 normotensive (Group 1), and 25 with OAG: 15 Primary Open-Angle Glaucoma (POAG) and 10 Exfoliation Glaucoma (EXG) (Group 2). Ophthalmic assessment included IOP measurements, ocular biometry, and anterior and posterior segment optical coherence tomography evaluation of the aforementioned ocular parameters, prior and 6 months after phacoemulsification surgery. Results: At the 6 months post-operative review, a greater IOP reduction was recorded in eyes with OAG, in comparison to normotensive ones (5.3mmHg and 1.6 mmHg respectively). In addition, a significant but similar increase was recorded in the values of the ACA, ACV, and ACD of both groups between the pre- and the post-op period. Furthermore, the CCT and AL values remained unaltered. Finally, there was a non-statistically significant change in the mean CMT and the mean average RNFL of both groups. Conclusion: Eyes with OAG tend to undergo a greater reduction in IOP post-phacoemulsification surgery, in comparison to normotensive eyes. This reduction may not be solely attributed to ocular anatomical changes after phacoemulsification surgery but may also be due to the remodeling of the trabecular meshwork and the ciliary body. This may be especially true in the case of OAG eyes, which already start off with a compromised trabecular endothelium prior to surgery.

c-FOS Expression Analysis in Pterygia Cell Spot Arrays.

BACKGROUND/AIM: Mechanisms of c-FOS activation in the onset and progression of pterygia remain under investigation. This study aimed to comparatively analyze c-FOS proto-oncogene expression levels in neoplastic pterygia and normal epithelia. MATERIALS AND METHODS: We used a liquid-based cytology assay on thirty (n=30) pterygia cell populations and normal epithelia (n=10) extracted by a smooth scraping of conjunctiva epithelia. Applying a cell spot-based technique, we constructed five (n=5) slides, each containing eight (n=8) cell spots. A modified immune-cytochemistry (ICC) assay for c-FOS protein was used. Additionally, digital image analysis was implemented to calculate c-FOS immunostaining intensity levels. RESULTS: High staining intensity levels of c-FOS were detected in 12/30 (40%), whereas the rest 18/30 (60%) demonstrated moderate expression. c-FOS levels were statistically significantly higher in the pterygia compared to control tissues (p=0.001). c-FOS levels in the pterygia were not associated with the sex of patients (p=0.678), the presence of recurrent lesion (p=0.390) or the location of the lesion (p=0.158). The levels of c-FOS, however, were marginally significantly affected by the morphology of the pterygia (p=0.005). More precisely, the c-FOS levels were significantly higher in pterygia with a fleshy morphology. CONCLUSION: c-FOS over-expression is observed frequently in pterygia. It seems to be critically involved in the molecular mechanism of the lesion by its over-expression affecting partially their morphological features. Cell spot liquid - based array analysis is an innovative, easy to implement technique for simultaneously evaluating a broad spectrum of molecules in multiple specimens on the same slide.

Kyrieleis Arteriolitis Associated with Acute Retinal Necrosis due to Herpes Simplex Virus Type 1 Secondary to Herpetic Encephalitis.

We report the case of a 52-year-old woman who presented to the emergency department with acute retinal necrosis in her left eye secondary to herpes simplex virus type 1 encephalitis for which she had been hospitalized four months before. Treatment with intravitreal foscarnet and intravenous acyclovir was promptly commenced followed by the addition of oral prednisolone. PCR analysis of aqueous humor detected HSV type 1 DNA. The condition responded to therapy with partial resolution of intraocular inflammation and improvement of visual acuity, but the presence of Kyrieleis plaques was observed two weeks after the initiation of treatment, when five intravitreal foscarnet injections had been administered. The patient was switched to oral therapy with valacyclovir, and 10 weeks after commencing treatment, the patient's left eye was free of inflammation, having achieved a BCVA of 20/20. Oral steroid treatment was gradually tapered off, and the patient was instructed to remain on prophylactic antiviral therapy. Kyrieleis arteriolitis is an uncommon finding in the context of acute retinal necrosis. As far as we are aware, we report the first case of Kyrieleis arteriolitis in acute retinal necrosis secondary to viral encephalitis and the second one presenting Kyrieleis plaques in acute retinal necrosis caused by herpes simplex virus type 1. Prior reports of cases of Kyrieleis arteriolitis in acute retinal necrosis are also presented.

Isolated optic neuritis after pembrolizumab administration for non-small-cell lung carcinoma.

PURPOSE: To report a case of isolated optic neuritis associated with pembrolizumab immunotherapy for metastatic non-small cell lung carcinoma. CASE PRESENTATION: A 76-year-old man, with a history of metastatic non-small cell lung carcinoma, presented with vision loss in his left eye for the past week. He had been treated with pembrolizumab for the underlying disease for 2 months. On presentation, best corrected visual acuity was 20/30 in the right eye and 20/200 in the left eye. Fundoscopy revealed optic nerve edema in the left eye. Visual fields examination in right eye revealed an enlarged blind spot and an extended defect in the inferior nasal quadrant. In the left eye a partial superior arcuate defect and an extended defect in the inferior hemisphere was observed. The mean deviation was -12.15 dB in the right eye and -13.70 dB in left eye. Pembrolizumab was withheld and corticosteroids were administered for a total of nine weeks, first intravenously and then slowly tapered orally, resulting in resolution of optic neuritis, restoration of visual acuity and in relative improvement in the visual field defects after 3 months. Calculated Naranjo Nomogram score was 7, indicating a 'highly probable' correlation. CONCLUSIONS: Optic neuritis is a relatively rare immune-related adverse event after exposure to checkpoint inhibitors cancer immunotherapy. Prompt discontinuation of the offending agent and early initiation of corticosteroid therapy is the mainstay of the treatment.

TWO-YEAR RESULTS OF INTRAVITREAL INJECTIONS OF AFLIBERCEPT IN COATS DISEASE: A CASE REPORT.

PURPOSE: To report long-term results of treatment with intravitreal injections of aflibercept in a newly diagnosed case of Coats disease. METHODS: An 18-year-old man presented to the retina clinic of our hospital complaining of blurred vision in the right eye for the past 3 months. His past medical and ocular history were unremarkable. The best-corrected visual acuity was 20/200 in the right eye and 20/20 in the left eye. Fundoscopy in the right eye revealed extensive macular edema with a circinate ring of hard exudates in the posterior pole temporally to the macula. Optical coherence tomography demonstrated macular edema with subretinal fluid. Peripheral telangiectasias and light bulb aneurysms in the inferior temporal arcade as well as in the nasal far periphery were found in the right eye in fluorescein angiography, confirming the diagnosis of stage 2B Coats disease. The left eye was normal. RESULTS: The original therapeutic strategy proposed was antivascular endothelial growth factor injections in the right eye, followed by laser photocoagulation. However, the patient did not consent to laser treatment and was treated with aflibercept monotherapy with 8 monthly intravitreal injections of aflibercept, followed by 6 injections every 2 months for a total of 14 injections over a period of 2 years. The best-corrected visual acuity in the right eye improved to 20/25 while optical coherence tomography imaging revealed significant decrease in retinal thickness with resolution of macular edema, and fluorescein angiography demonstrated prominent regression of aneurysms and leakage. CONCLUSION: To the best of our knowledge, this is the first case treated with aflibercept monotherapy, suggesting the significant role of vascular endothelial growth factor in vascular permeability in Coats and supporting the rationale that antivascular endothelial growth factors are a valuable therapeutic option for Coats disease.

Short-term effect of non-preserved cationic oil-in-water ophthalmic emulsion on tear meniscus parameters of healthy individuals in a prospective, controlled pilot study.

Background: This study investigated the effect of instilling a single drop of non-preserved cationic oil-in- water ophthalmic emulsion (Cationorm®) on the lower (LTM) and upper tear meniscus (UTM) parameters of normal eyes. Methods: In this prospective, single-center, non-randomized, controlled pilot study, optical coherence tomography was used to estimate the UTM and LTM height, depth, and cross-sectional area in participants without a history of dry eye disease. In the right eye (study eye), we instilled one drop of Cationorm® in the lower conjunctival sac. Scans of the tear menisci were acquired at baseline, before the instillation, and at 5, 15, and 30 min thereafter. Control scans of the left eye (control eye) were obtained at the same timepoints. The tear meniscus parameters of the study eye were compared with the control eye at each timepoint. Results: Twenty subjects (11 male and 9 female; mean [standard deviation] of age: 37.8 [10.9] years) were included in the study. Compared to the control eye, instillation of a single drop of Cationorm® resulted in significantly higher LTM parameter values and a higher UTM cross-sectional area up to 30 min after instillation (all P < 0.05). The UTM height and depth were significantly greater in the study eye than in the control eye up to 5 min (P < 0.001 and 0.007, respectively) and 15-min (P = 0.045, and 0.002, respectively) after Cationorm® instillation. In the study eye, Cationorm® resulted in a significant increase in LTM parameter values up to 30 min post-instillation (all P < 0.001). The UTM height was significantly greater up to 15 min post-instillation than at baseline. The UTM depth and area increased significantly from baseline to 5 min after instillation (P = 0.043, and 0.002, respectively). Conclusions: Cationorm® seems to have a prolonged residence time on the ocular surface of healthy subjects as indicated by LTM parameters and to a lesser extent by UTM parameters.

Effect of Intravitreal Injection of Aflibercept on Cardiovascular Risk Parameters in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: Systemic administration of anti-Vascular Endothelial Growth Factors (anti- VEGFs) has been associated with severe cardiovascular adverse events in oncologic patients. The purpose of this pilot study is to evaluate the short-term effect of a single intravitreal injection of aflibercept on biomarkers related to increased risk of cardiovascular disease. PATIENTS AND METHODS: Forty-seven treatment naïve patients with neovascular age-related macular degeneration in one eye were enrolled in the study. The patients underwent treatment with one intravitreal injection of aflibercept in the affected eye. Laboratory biomarkers of cardiovascular disease were evaluated before the first intravitreal injection of aflibercept and at 7 and 30 days after aflibercept administration. More precisely, we evaluated the levels of homocysteine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Creactive protein. RESULTS: There was not any statistically significant change in the levels of the evaluated parameters up to one month after the first intravitreal injection of aflibercept. CONCLUSION: According to our study, the administration of a single dose of aflibercept in eyes with neovascular age-related macular degeneration does not seem to affect the evaluated biomarkers that are related to cardiovascular disease.

Choroidal Thickness Evaluation in a Transfusion-Dependent Beta-Thalassemia Greek Population.

PURPOSE: To evaluate choroidal thickness in a group of beta-thalassemia patients as assessed by enhanced depth imaging optical coherence tomography. PATIENTS AND METHODS: This single-center, observational study involved transfusion-dependent beta-thalassemia (TD-ß-thal) patients and healthy controls. One eye of each participant was included in the study. Submacular and peripapillary choroidal thickness, as well as central macular thickness and retinal nerve fiber layer thickness, were evaluated. RESULTS: Thirty-eight TD-ß-thal patients (mean age 42 ± 10.7 years) and 22 healthy controls (mean age 40.3 ± 10.2 years) were included in the study. Subfoveal choroidal thickness was 297.4 ± 74.5 µm in the patient group and 358.4 ± 71.4 µm in the control group (p=0.003). Overall, in the submacular area, the choroid was found to be significantly thinner in the beta-thalassemia population compared to controls in all evaluated points, except for the spot located 1500 µm nasally to the fovea (p=0.093). In the peripapillary area, choroidal thickness was also significantly lower in the thalassemic population compared to the controls (nasal p=0.033, temporal p=0.01, superior p=0.01), except for the inferior quadrant (p= 0.191). We did not observe statistically significant differences in the retinal nerve fiber layer thickness and the central macular thickness between the two groups (p=0.658 and p=0.276, respectively). No correlations with hemoglobin, serum ferritin or iron levels emerged. Patients with the intermediate subtype appeared to have significantly thinner choroids than the ones with thalassemia major. CONCLUSION: Our findings suggest that choroidal thickness in the submacular and peripapillary area is significantly reduced in thalassemic patients, compared to healthy individuals. Choroidal thinning in beta-thalassemia possibly reflects the effect of chronic anemia and underlying hemodynamic changes on choroidal tissue.

The Acute Effects of Electronic Cigarette Vaping and Tobacco Cigarette Smoking on Choroidal Thickness in Young, Healthy, Habitual, Dual Smokers.

The present study aims to evaluate and compare the acute effects of tobacco cigarettes (TC) smoking and electronic cigarette (EC) vaping on foveal and choroidal thickness (CT) in young, healthy, dual smokers. Participants underwent four trials: 5 min TC; 5 min EC; 30 min EC; and 60 min nothing (sham trial). Scans before and immediately after each trial were obtained using spectral domain optical coherence tomography with the enhanced depth imaging mode. Changes in central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and CT at fourother points, 500 µm and 1000 µm temporally and nasally to the fovea, were measured. Forty-seven participants (33 male, 14 female; mean age 24.85 ± 1.57 years) were included. They smoked 13.53 ± 5.27 TCs/day for 6 ± 2.3 years and vaped ECs for the past 2.4 ± 1.08 years. We did not observe any statistically significant change in SFCT, CFT, and CT of the other points after any of the fourtrials. The acute changes in CFT and CT after EC vaping or TC smoking did not differ significantly compared to the sham trial. Smoking and vaping does not seem to result in statistically significant acute alterations in foveal and CT in young, dual smokers.

Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration.

PURPOSE: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. METHODS: Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. RESULTS: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. CONCLUSION: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. CLINICALTRIALSGOV ID: NCT03509623.

Late-Onset Bilateral Choroidal Metastases from Clear Cell Renal Cell Carcinoma.

AIM: To present a case of clear cell renal cell carcinoma with late-onset bilateral choroidal metastases. Case Report. A 57-year-old male patient in the Oncology Clinic complained of reduced vision in the right eye (OD) for 7 days. The patient, who was under immunotherapy with nivolumab, had been diagnosed with clear cell renal cell carcinoma in the left kidney 15 years ago that recurred in the right kidney before 2 years. Metastases in the brain, lungs, and bones had also been diagnosed. On ophthalmological examination, the visual acuity was 20/50 OD and 20/20 in the left eye (OS). Dilated fundus examination in OD revealed a single raised oval-shaped yellowish choroidal nodule infratemporally with macular involvement. A similar lesion, sparing the macula, was observed in OS. Fundus autofluorescence revealed diffuse punctate hyperautofluorescence on the lesions. Serous macular detachment was also observed in OD. A standardized A-scan ultrasound demonstrated an irregular structure of the lesions with moderate to high internal reflectivity. Based on the history and clinical and echographic characteristics, the diagnosis of bilateral choroidal metastases from renal cell carcinoma was set. CONCLUSION: Choroidal metastases from the primary renal tumor are extremely rare. The time interval between primary malignancy and choroidal metastasis is reported to be 12-96 months. Bilateral choroidal metastases have been described in 9 cases. We describe a rare case where bilateral choroidal metastases were diagnosed 15 years after the initial diagnosis of clear cell renal cell carcinoma.

Comparison of intraocular pressure using Goldmann applanation tonometry versus non-contact tonometry in eyes with high-viscosity silicone oil.

BACKGROUND: To compare intraocular pressure (IOP) measurements using Goldmann applanation tonometer (GAT) and air tonometer (non-contact tonometry [NT]) in vitrectomized eyes with high-viscosity silicone oil tamponade, as well as in normal eyes. PATIENTS AND METHODS: In this prospective comparative study, 32 eyes with silicone oil tamponade of high viscosity (5700 CS) and 32 normal fellow eyes were included. IOP was measured by GAT and air tonometer 30 ± 12 days after vitrectomy, while measurements of central corneal thickness (CCT) were also obtained. RESULTS: In eyes with silicone oil, IOP was 20.09 ± 4.91 mmHg and 16.75 ± 3.86 mmHg using contact tonometer and air tonometer, respectively (p < 0.0001). In normal eyes, IOP was 16.41 ± 2.15 mmHg and 16.31 ± 2.49 mmHg using the same tonometry techniques and this difference was not statistically significant (p = 0.598). In addition, no significant correlation was detected between IOP measurements using both techniques and age, gender, CCT, and type of lens. CONCLUSIONS: It seems that GAT overestimates IOP in eyes with high-viscosity silicone oil compared with NT, while both IOP measurement techniques in normal eyes provide similar values. Further assessment of available IOP measurement methods could possibly establish the most accurate technique for IOP estimation in vitrectomized eyes with silicone oil tamponade.

Brinzolamide-brimonidine fixed combination for the prevention of intraocular pressure elevation after phacoemulsification.

AIM: To evaluate the effectiveness of brinzolamide-brimonidine fixed combination to control the intraocular pressure elevation throughout the first 24 h following uncomplicated phacoemulsification cataract surgery. PATIENTS AND METHODS: A total of 62 patients who underwent phacoemulsification cataract surgery were included in this prospective randomized comparative case series. The brinzolamide-brimonidine fixed combination group (34 eyes) was administered a single dose of brinzolamide-brimonidine fixed combination immediately after phacoemulsification. No treatment was administered in the control group (28 eyes). Intraocular pressure was measured 1 day before surgery (baseline) and at 6, 12 and 24 h postoperatively. RESULTS: The brinzolamide-brimonidine fixed combination group had significantly lower intraocular pressure at 6, 12 and 24 h after phacoemulsification compared to baseline (p < 0.0001 for all comparisons), while in control group, intraocular pressure was significantly higher at 6 and 12 h after surgery compared to baseline (p < 0.001 and p < 0.0001, respectively). In control group, an intraocular pressure elevation ⩾ 5 mm Hg was noted in 32.4% of the eyes at 6 and 12 h and in 5.9% of eyes at 24 h after surgery, while in brinzolamide-brimonidine fixed combination group, only 8.8% of the eyes at 6 h postoperatively had such an intraocular pressure elevation. CONCLUSION: The administration of a single drop of brinzolamide-brimonidine fixed combination effectively prevented intraocular pressure elevations and intraocular pressure spikes during the first 24 h after uneventful phacoemulsification.

Effect of a single session of micropulse laser trabeculoplasty on corneal endothelial parameters.

BACKGROUND: To evaluate the effect of a single session of micropulse laser trabeculoplasty on the cornea in eyes with primary open-angle glaucoma and pseudoexfoliation glaucoma. METHODS: This single-centre, prospective, case series enrolled patients with primary open-angle and pseudoexfoliation glaucoma under treatment with glaucoma agents that required additional intraocular pressure reduction. Eyes underwent 360 degrees treatment with 532 nm micropulse laser trabeculoplasty. Central corneal thickness, endothelial cell count, hexagonal cell ratio and co-efficient of variation of endothelial cells were measured before micropulse laser trabeculoplasty and at one, three and six months after treatment. RESULTS: Twenty eyes of 20 patients (mean age 67.6 ± 8.0 years) with primary open-angle glaucoma and 18 eyes of 18 patients (mean age 71.44 ± 6.43 years) with pseudoexfoliation glaucoma were included in the study. Treatment with micropulse laser trabeculoplasty resulted in statistically significantly lower intraocular pressure compared to baseline in both primary open-angle and pseudoexfoliation glaucoma eyes (p < 0.0001 at both comparisons). Central corneal thickness, endothelial cell count, hexagonal cell ratio and co-efficient of variation of the endothelial cell size showed no significant change between baseline and six months after micropulse laser trabeculoplasty in both primary open-angle and pseudoexfoliation glaucoma eyes. CONCLUSION: A single session of micropulse laser trabeculoplasty did not affect central corneal thickness and corneal endothelium parameters in eyes with primary open-angle and pseudoexfoliation glaucoma.

Bacteriology and Antimicrobial Susceptibility Patterns of Childhood Acute Bacterial Conjunctivitis in Western Greece.

Acute bacterial conjunctivitis is a common, highly contagious infection in children and is usually treated empirically with broad spectrum topical antibiotics. In the current study we investigated bacteriology and antibiotic susceptibility patterns in childhood acute bacterial conjunctivitis in Western Greece. We conducted a retrospective analysis of presumed acute bacterial conjunctivitis cases in ''Karamandaneio'' Pediatric General Hospital of Patras, Western Greece, between February 1, 2013 and January 31, 2018. Specimens from the lower conjunctiva fornix were isolated from 191 cases and outcomes were analyzed to identify the pathogenic bacteria of acute bacterial conjunctivitis and their corresponding antibiotic susceptibility patterns. Patients were divided into 3 groups; Group A included neonates under 28 days of life, Group B children from 1 month to 2 years and Group C from 2 years to 14 years. Results revealed that Staphylococcus spp., Haemophilus spp. and Streptococcus spp. were the most prevalent pathogens. No significant differences in isolated pathogens were found between the age groups. Antibiotic resistance rates were higher against ampicillin, ceftriaxone, ceftazidime and sulfamethoxazole. Resistance rates to Ciprofloxacin were low while none of the evaluated isolates were resistant to vancomycin. We concluded that predominant pathogens of childhood acute bacterial conjunctivitis in Western Greece were Staphylococcus spp., Haemophilus spp. and Streptococcus spp. Continuous surveillance, focused in distinct geographic areas, is encouraged to prepare more precise protocols of empirical treatment.

Visual and anatomic outcomes of aflibercept treatment in treatment-naive patients with neovascular age-related macular degeneration; real-life data over 24 months.

PURPOSE: The aim of this study is to evaluate the 2-year visual and anatomic results of treatment with intravitreal injections of aflibercept in newly diagnosed, treatment-naive patients with neovascular age-related macular degeneration in routine clinical practice of a tertiary hospital of Southwestern Greece. METHODS: In this retrospective, single-center, non-randomized case-series study we analyzed the records of 32 treatment-naive eyes of 28 patients treated with intravitreal injections of aflibercept. Patients received treatment in the Department of Ophthalmology of the University Hospital of Patras from January 2017 to August 2019. The scheduled treatment regimen included a loading dose of 3 consecutive monthly injections of aflibercept and then injections at 8-week intervals for the next 9 months followed by a treat and extend treatment during the second year. Data such as age, gender, best corrected visual acuity (BCVA) and number of injections were recorded. Spectral domain optical coherence tomography (SD-OCT) findings including presence or absence of fluid and automated central macular thickness measurement at baseline, 12 and 24 months were also recorded. RESULTS: The mean age of the patients (14 male, 14 female) was 78.5±7.73 years. Over a period of 12 months, and after a median number of 6 visits (range 3-10), patients received a median number of 6 intravitreal injections of aflibercept (range 3-8). Twenty eyes completed 2 years of treatment with aflibercept. Over the 2-year period patients conducted a median of 14 visits (range 9-15) and received a median number of 10 IVAs (range 6-13). The median logMAR BCVA at 12 months was significantly better compared to baseline [0.412 (range 0.046-1.097) versus 0.549 (range 0-1.301) respectively; p=0.003] while median logMAR BCVA at 24 months [0.398 (range 0.222-1.097)] did not differ significantly compared to baseline (p=0.295). The central macular thickness at baseline was 398.75±98.16 µm and decreased statistically significantly at 12 (295.81±80.48 µm) and 24 months (289.29±34.25 µm) compared to baseline (p=0.0002 and p=0.002, respectively). At baseline SD-OCT examination subretinal fluid (SRF) was present in 26 eyes (81.25%), intraretinal fluid (IRF) was present in 20 eyes (62.5%) while pigment epithelium detachment (PED) was observed in 28 eyes (87.5%) At 12 months SRF was present in 16 eyes (50%), IRF was present in 10 eyes (31.25%) while PED was observed in 23 eyes (71.88%). At 24 months examination SRF was present in 4 eyes (20%), IRF was present in 10 eyes (50%) while PED was observed in 14 eyes (70%). No serious adverse events occurred during this period. CONCLUSION: Treatment with intravitreal injections of aflibercept in a real life setting resulted in a significant improvement in BCVA at 12 months and in a significant anatomic restoration throughout the 24-month follow-up.

Functional and anatomic results of up to 24 months aflibercept treatment for diabetic macular edema in real-life setting.

PURPOSE: Treatment with intravitreal injections of anti-vascular endothelial growth factors, like aflibercept, has revolutionized the management of diabetic macular edema. The purpose of this study is to evaluate the 2-year results of treatment with aflibercept in newly diagnosed, treatment-naive patients with diabetic macular edema in a real-life setting in a tertiary hospital of Southwestern Greece. METHODS: In this retrospective, real-life, single-center, cohort study the records of diabetic patients were reviewed. In the study we included treatment naive eyes that started treatment with intravitreal injections of aflibercept in the Department of Ophthalmology of the University Hospital of Patras. The scheduled treatment regimen of aflibercept was based on the Summary of Product Characteristics of the product and included a loading dose of 5 monthly aflibercept injections followed by bimonthly treatment until the completion of the first year. During the second year a treat and extend treatment regimen was applied. We recorded data such as age, gender, number of visits and injections, best corrected visual acuity (BCVA) and central macular thickness (CMT) as it was evaluated by a spectral domain optical coherence tomography (SD-OCT). RESULTS: Thirty treatment-naive eyes of 22 patients (14 male, 8 female) received treatment with aflibercept for at least 1 year during the period between January 2017 and August 2019. The mean age of the patients was 68.64±7.35 years. Ninety percent of the patients suffered from type-II diabetes and 9% from type-I. The median time between the diagnosis of diabetic macular edema and initiation of treatment with intravitreal injections of aflibercept was 0.5 months (range 0-3 months). Median baseline logMAR BCVA was 0.398 (range 0.046-1.301). The mean CMT at baseline was 388.0±162.94µm. Over a period of 12 months, and after a mean number of 7.5±2.3 visits, patients received a mean number of 7±1.12 intravitreal injections of aflibercept. Eighteen eyes (60%) received an induction phase with 5 monthly injections according to aflibercept SPC. After 12 months the median BCVA (0.324, range 0.0-1.3) was statistically significantly better compared to baseline (p=0.024) and the CMT (295.67±70.99) was significantly lower compared to baseline (p=0.017). Eighteen eyes (60%) completed 2 years of treatment with aflibercept. Over the 2-year period patients made a mean number of 12.7±3.08 visits and received a mean number of 10.2±1.64 intravitreal injections of aflibercept. The median logMAR BCVA at 2 years (0.301, range 0-0.52) was statistically significantly better compared to baseline (p=0.013) and the CMT (293.53±65.93) was significantly lower compared to baseline (p=0.01). No serious adverse events were recorded during this period. CONCLUSION: Aflibercept resulted in significant functional and anatomic improvement after 12- and 24-month treatment in diabetic macular edema eyes in a real-life setting. The majority of the eyes completed the 2-year treatment regimen of aflibercept.

Expression and Localization of Glycosaminoglycans/Proteoglycan in Pterygium: An Immunohistochemical Study.

Pterygium is a triangle-shaped fibrovascular hyperplasia of the bulbar conjunctiva on the cornea. The purpose of this study was to analyze Proteoglycans (PGs) by Immunohistochemistry (IHC) in pterygium tissues and to compare the results with normal conjunctiva. Twenty-four patients (14 males) undergoing primary pterygium excision and 17 healthy individuals (10 males), undergoing extracapsular cataract surgery, were included. Pterygium tissues and normal conjunctiva tissues were surgically removed. The tissue sections were fixed in 2% paraformaldehyde and incubated with monoclonal antibodies against PGs anti-mouse IgG. Immunohistochemical study showed stronger expression of keratan sulfate in the stroma of the pterygium compared to normal conjunctiva. An increased expression of heparan sulfate was observed in the epithelial layer and around the pterygium vessels. On the other hand, dermatan sulfate showed an increased expression and localization not only in the sub-epithelial area of the pterygium and normal conjunctiva, yet throughout the stroma of the pterygium. The differences in the expression and localization of the studied extracellular matrix proteoglycans in the pterygium tissue compared to normal conjunctiva may explain the tissue hyperplasia, structure, and the functional properties in pterygium.

Dexamethasone implant for immunogammopathy maculopathy associated with IgA multiple myeloma.

BACKGROUND: We describe a case where hyperviscosity retinopathy and immunogammopathy maculopathy were the presenting features of IgA multiple myeloma and report the response of maculopathy to intravitreal injection of dexamethasone implants. CASE PRESENTATION: A 56-year-old man presented at the Department of Ophthalmology with the chief complain of reduced vision for the past 10 days in both eyes. Ophthalmic examination revealed central retinal vein occlusion resembling signs with severe macular edema in both eyes with prominent serous macular detachment. After comprehensive evaluation, an IgA type kappa multiple myeloma was diagnosed complicated with hyperviscosity-associated retinopathy and immunogammopathy maculopathy. Patient was treated with multiple sessions of plasmapheresis, systemic chemotherapy, and finally intravitreal implants of dexamethasone with complete restoration of macular edema and serous macular detachment in both eyes. The visual function and the hyperviscosity-associated retinopathy were partially restored. CONCLUSION: Ocular manifestation might be the only presenting sign of a life-threatening disease such as IgA multiple myeloma. A high level of suspicion is required to diagnose and treat such cases promptly and effectively.