A 52-Year-Old Man with Aneurysmal Subarachnoid Hemorrhage Associated with Delayed-Onset Vitreous Hemorrhage (Terson's Syndrome) Successfully Treated with Balloon-Assisted Coiling and Delayed Vitrectomy.

BACKGROUND Terson's syndrome (TS) is a medical condition characterized by intraocular bleeding that can lead to visual impairment and is associated to subarachnoid hemorrhage (SAH). The pathophysiology and natural history are not well established in the current literature. This report describes successful treatment of a 52-year-old man with aneurysmal SAH who developed late-onset TS using balloon-assisted coiling and vitrectomy to raise awareness of this important complication of aneurysmal SAH. CASE REPORT A 52-year-old smoker with no known past medical history presented to the emergency department with a sudden, severe headache that worsened with photophobia and phonophobia. The patient had a diffuse SAH and underwent an embolization procedure. After 48 hours of close Intensive Care Unit monitoring, the patient's vital signs were stable, and the GCS score was consistently 15/15. However, after 3 weeks in the hospital, the patient experienced blurred vision and a right upper quadrantanopia. Further examination revealed TS and the patient underwent a vitrectomy in 1 eye. The surgery was successful and the eye recovered to 20/20 with no complications. However, the other eye showed slow absorption of the hemorrhage, and a vitrectomy was scheduled for that eye as well. CONCLUSIONS TS is a complication of aneurysmal SAH that can lead to vision loss and increased morbidity. It often goes undiagnosed, and ophthalmologists are not regularly consulted. Late manifestation of the condition is exemplified by the present case. Early detection and intervention are crucial for better patient outcomes.

Silicone oil insulation effects on flash electroretinogram and visual evoked potential in patients with retinal detachment.

BACKGROUND: Silicone oil is used as endotamponade following vitreoretinal surgery to maintain the retina reattached when indicated. This study investigates the hypothesis that silicone oil causes insulation effects on the retina by affecting its response to light. METHODS: Electrophysiological responses to a flash stimulus were recorded using full-field electroretinography (ERG) and visual evoked potentials (VEP). Recordings were performed in 9 patients who underwent surgery for retinal detachment, before (1-2 days) and after (2-3 weeks) silicone oil removal (SOR) in both the study and the control eye. Flash ERG and VEP recordings were performed according to the ISCEV standard protocol. RESULTS: Statistically significant differences were found in the study eye in the amplitudes of the ERG responses and their corresponding ratios, i.e. the amplitude after SOR over the amplitude before SOR, in all conditions tested. No differences were observed in the control eye. The mean ratio of photopic ERG response was 3.4 ± 2.4 for the study and 1.0 ± 0.3 for the control eye (p<0.001). The mean ratio of ERG flicker response was 3.1 ± 2.4 and 1.0 ± 0.3, respectively (p = 0.003). Scotopic flash ERG ratio was 5.0 ± 4.4 for the study and 1.3 ± 0.6 for the control eye (p = 0.012). No differences were observed for the amplitude and latency of flash VEP response after SOR. CONCLUSIONS: Silicone oil causes a reduction in flash ERG responses; no effect was found on flash VEP responses. ERGs in eyes filled with silicone oil should not be considered representative of retinal functionality, in contrast to VEPs, which are not affected by silicone oil presence.

Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes.

PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD). METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA. RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study's follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p < 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p < 0.001), eye (p = 0.003), and time-eye interaction (p < 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (p = 0.015). CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.

High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete: Genetic Heterogeneity and Distinct Phenotypes.

Background and Objectives: Our goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece. Methods: We aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993-2019), were found to carry a pathogenic TTR variant. Results: Over the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18-37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54-78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants. Discussion: Our study revealed that the prevalence of hATTR in Crete is one of the world's highest. Three different pathogenic TTR variants causing distinct clinical phenotypes were identified in this relatively small population pool.

A Real-World, Multicenter, 6-Month Prospective Study in Greece of the Effectiveness and Safety of Ranibizumab in Patients with Age-Related Macular Degeneration Who Have Inadequately Responded to Aflibercept: The "ELEVATE" Study.

Purpose: Real-world evidence on short-term outcomes of ranibizumab in wet age-related macular degeneration (wAMD) following inadequate response to aflibercept is scarce. This study aimed to evaluate the functional and anatomic effects of switching to ranibizumab in cases of wAMD previously treated with aflibercept with inadequate response. Patients and Methods: Prospective, observational study performed in eight ophthalmology hospital/private clinics in Greece, enrolling consented patients with active wAMD, ≥50 years-old, who had initiated ranibizumab ≥28 days and <2 months after their last aflibercept injection. Data were collected at enrollment, and at 1, 3 and 6 months post-treatment onset (post-baseline). Results: Between September-2015 and November-2017, 103 eligible patients (56.3% females; mean age: 74.8±8.6 years) were consecutively enrolled. The age at AMD diagnosis in the study eye was 71.3±8.8 years. Aflibercept (median of 5 injections received over 11.3 months) had been discontinued for anatomical (in 69.9%) and/or functional (38.8%) reasons. At baseline (median: 24.3 months after wAMD diagnosis), choroidal neovascularization was occult in 69.1% of evaluable study eyes; 60.2% of the study eyes had pigment epithelial detachment (PED); 42.7% cysts; 21.4% fibrosis; 66.0% subretinal, and 59.2% intraretinal fluid. At 6 months post-baseline: a median of 3 ranibizumab injections (range: 1-6) had been received; the best-corrected visual acuity (BCVA)≥0 letter gain rate was 81.8%; the BCVA ≥15 letter gain rate was 17.0%; BCVA gain was 3.2 letters [mean increase: 3.2±10.0 letters; median: 0.0; p = 0.002]; PED greatest basal diameter (GBD; median: 1470.5 µm) also decreased (median decrease: 114.0 µm; p = 0.019). Baseline central retinal thickness (CRT; median: 312.0 µm) remained unchanged. One patient permanently discontinued ranibizumab due to adverse event occurrence, assessed as not causally related to ranibizumab. There were no ranibizumab-related adverse reactions. Conclusion: Six-month treatment with ranibizumab in aflibercept inadequate responders led to visual acuity and PED GBD improvements, with no statistically significant CRT change.

Progression of Macular Atrophy in Patients Receiving Long-Term Anti-VEGF Therapy for Age-Related Macular Degeneration: Real-Life Data.

PURPOSE: This study aimed to evaluate the progression of macular atrophy (MA) based on near-infrared reflectance (NIR) and optical coherence tomography (OCT) images, in patients with age-related macular degeneration (AMD), receiving anti-vascular endothelial growth factor (anti-VEGF) treatment for at least a 6-year period. MATERIALS AND METHODS: This retrospective study included 53 naïve patients (53 eyes) with neovascular AMD from 2 centers, who were treated with anti-VEGF intravitreal injections and had no MA at baseline. MA was evaluated in an annual basis using NIR images, while all available OCT images were used to confirm that the atrophic area fulfilled the criteria proposed by the Classification of Atrophy Meetings (CAM) group for complete retinal pigment epithelium and outer retinal atrophy. Incidence and progression of MA were evaluated. Associations with best-corrected visual acuity (BCVA) and total number of injections were also studied. RESULTS: Treatment duration of our patients was 7.34 ± 1.54 years. The mean number of anti-VEGF injections was 24.4 ± 13.6. BCVA at baseline was 0.38 ± 0.27 logMAR, while at the final visit, it was 0.60 ± 0.35 logMAR (p = 0.731). The cumulative incidence of new MA at years 1, 2, 3, 4, 5, and 6 was 1.89%, 18.87%, 32.08%, 39.62%, 49.06%, and 50.94%, respectively. In patients who developed MA, mean MA area increased from zero at baseline to 5.66 ± 7.18 mm2 at the final visit. The estimated annual enlargement of MA was 0.45 mm/year based on square root transformation (1.12 mm2/year, untransformed data). MA progression does not appear to be significantly associated with age (R = 0.055; p = 0.784), gender (R = 0.113; p = 0.576), BCVA (R = 0.168; p = 0.404), and total number of injections (R = 0.133; p = 0.255). CONCLUSION: In this real-life setting, half of the neovascular AMD patients under anti-VEGF treatment, without MA at therapy initiation, developed MA over a period of at least 6 years. In this work, the number of injections did not seem to have a significant association with MA progression.

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

PURPOSE: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement. METHODS AND MATERIALS: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion. RESULTS: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively. CONCLUSIONS: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.

Efficacy of Topical Nepafenac 0.3% in the Management of Postoperative Cystoid Macular Edema.

PURPOSE: To assess the effect of twice-daily nepafenac ophthalmic suspension 0.3% on postoperative cystoid-macular-edema (CME). PATIENTS AND METHODS: In this prospective, clinic-based, non-randomized case-series, 21 patients (21 eyes) were enrolled with either acute or chronic postoperative CME after cataract extraction. Patients were treated with twice-daily nepafenac 0.3% drops, and followed for at least a 4-month period. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT)-derived central retinal thickness (CRT) were measured. RESULTS: From 21 patients, eight presented with acute postoperative CME and 13 with chronic CME. Mean follow-up was 4.82±1.24 months. No adverse events were reported during the study. Baseline BCVA was 0.49±0.36 logMAR and improved to 0.36±0.42 logMAR at the last follow-up visit (P<0.005). CRT decreased from 450.40±90.74 µm at baseline to 354.60±81.49 µm (P<0.05), following treatment. CONCLUSION: Our outcomes strongly suggest that administrating nepafenac 0.3% drops on a twice-daily regimen could be a promising alternative for the management of postoperative CME. Additional studies are necessary to further validate our results.

Comparison of the Efficacy of Brolucizumab with Natural Disease Progression in Wet AMD Using Clinical Data from the Phase III HAWK and HARRIER Trials and Modelled Placebo Data.

Aim: To compare the treatment effect of brolucizumab, a novel anti-vascular endothelial growth factor therapeutic, with a putative placebo in patients with wet age-related macular degeneration. Materials and Methods: Clinical treatment-effect data from patients receiving brolucizumab 6 mg in the HAWK and HARRIER studies were compared with modelled placebo data using a previously developed and validated indirect response, non-linear, mixed effects model describing the natural visual acuity decline in wet age-related macular degeneration. The placebo model incorporated patient-level data from the sham injection arms of the MARINA and PIER studies, corrected for baseline best corrected visual acuity and age difference between these studies and the HAWK and HARRIER studies. Results: Compared with a modelled placebo, brolucizumab treatment was associated with an overall best corrected visual acuity gain of approximately 22 Early Treatment Diabetic Retinopathy Study letters at Week 48 and 28 letters at Week 96. Conclusions: As anti-vascular endothelial growth factor therapy is now a standard of care for wet age-related macular degeneration, it is not feasible to conduct placebo-controlled trials for new wet age-related macular degeneration treatments. By allowing comparison with the natural decline in visual acuity without treatment, this analysis conveys the clinical importance of brolucizumab for the treatment of wet age-related macular degeneration.

Nonresponders to Ranibizumab Anti-VEGF Treatment Are Actually Short-term Responders: A Prospective Spectral-Domain OCT Study.

PURPOSE: To investigate the inter-individual variability in duration of anti-vascular endothelial growth factor (VEGF) treatment effect in neovascular age-related macular degeneration (nvAMD). DESIGN: Prospective observational multi-centered study. PARTICIPANTS: Forty-eight patients with nvAMD treated with anti-VEGF injections were included. Both treatment naive (n=25) as well as patients who had previously received treatment with ranibizumab (n=23) more than one month prior to their enrollment were recruited. METHODS: Patients received injection with ranibizumab (0.5 mg/0.05 ml) and were followed weekly for 4 weeks with spectral-domain OCT (SD-OCT) assessing the time to maximal reduction of central retinal thickness (CRT) and the presence of intraretinal and subretinal fluid. Other data collected included age, gender, visual acuity, axial length, lens status, and previous injections. The Shapiro-Wilk test was used to examine normal distributions for all variables. Correlations were examined by calculating Spearman's correlation coeficient. Distributions of quantitative variables are described as means (±SD). Qualitative variables are summarized by counts and percentage. MAIN OUTCOME MEASURES: Time to maximal reduction of CRT and intra- and subretinal fluid after ranibizumab injection. RESULTS: A total of 48 eyes of 48 patients (age 74.8±8.3 years, 62.5% female, 52% treatment naive, 35.4% pseudophakic) were assessed. Two-thirds (64.6%) reached maximal CRT reduction earlier than the standard 4-week interval: 6.3% at 1 week postinjection, 22.9% at 2 weeks postinjection, and 35.4% at 3 weeks postinjection. Only 35.4% of patients had maximal CRT reduction at 4 weeks. Twenty percent of treatment-naive and 34.8% of non-naive patients had a week-4 CRT that was >35 µm thicker than the earlier occuring lowest CRT value (nadir). The time to maximal CRT reduction was not related to axial length, age, lens status, or history of injections. CONCLUSIONS: Optimal dosing interval for maximal CRT reduction may be less than 4 weeks for a significant proportion of patients. Most patients will be classified as complete responders if intervals less than 4 weeks are used to assess anti-VEGF treatment response. Disease load rather than eye size appears to be the driver of anti-VEGF treatment duration and therefore, dosing interval needs to be optimized in the cohort of short-term responders.

Long-term Comparison of Combined t-PTK and CXL (Cretan Protocol) Versus CXL With Mechanical Epithelial Debridement for Keratoconus.

PURPOSE: To compare the long-term outcomes of corneal cross-linking (CXL) for the treatment of keratoconus using two different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) and mechanical epithelial debridement. METHODS: In this prospective, comparative, interventional case series, 26 patients (30 eyes) with progressive keratoconus underwent CXL treatment. Fifteen eyes (13 patients) underwent epithelial removal with t-PTK (Cretan protocol) and 15 eyes (13 patients) underwent mechanical epithelial debridement (Dresden protocol) during CXL. Visual, refractive, and keratometric outcomes were evaluated preoperatively and at 1, 2, 3, and 4 years postoperatively. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. In the Cretan protocol group, mean uncorrected (UDVA) and corrected (CDVA) visual acuity improved from 0.99 ± 0.42 and 0.33 ± 0.28 logMAR preoperatively to 0.75 ± 0.32 (P = .018) and 0.21 ± 0.16 (P = .024) logMAR at 4 years postoperatively, respectively. In the Dresden protocol group, mean UDVA improved from 0.83 ± 0.47 logMAR preoperatively to 0.63 ± 0.40 logMAR (P = .033) at 4 years postoperatively, whereas mean CDVA did not demonstrate a statistically significant improvement postoperatively (P > .05). In the Cretan protocol group, mean corneal astigmatism improved from -6.19 ± 4.54 diopters (D) preoperatively to -4.68 ± 3.10 D (P = .041) at last follow-up, whereas in the Dresden protocol group there was no statistically significant difference postoperatively (P > .05). CONCLUSIONS: Epithelial removal with t-PTK during CXL (Cretan protocol) resulted in better visual, refractive, and keratometric outcomes compared with mechanical epithelial debridement over a long-term follow-up. [J Refract Surg. 2019;35(10):650-655.].

Effects of BNN27, a novel C17-spiroepoxy steroid derivative, on experimental retinal detachment-induced photoreceptor cell death.

Retinal detachment (RD) leads to photoreceptor cell death secondary to the physical separation of the retina from the underlying retinal pigment epithelium. Intensifying photoreceptor survival in the detached retina could be remarkably favorable for many retinopathies in which RD can be seen. BNN27, a blood-brain barrier (BBB)-permeable, C17-spiroepoxy derivative of dehydroepiandrosterone (DHEA) has shown promising neuroprotective activity through interaction with nerve growth factor receptors, TrkA and p75NTR. Here, we administered BNN27 systemically in a murine model of RD. TUNEL+ photoreceptors were significantly decreased 24 hours post injury after a single administration of 200 mg/kg BNN27. Furthermore, BNN27 increased inflammatory cell infiltration, as well as, two markers of gliosis 24 hours post RD. However, single or multiple doses of BNN27 were not able to protect the overall survival of photoreceptors 7 days post injury. Additionally, BNN27 did not induce the activation/phosphorylation of TrkAY490 in the detached retina although the mRNA levels of the receptor were increased in the photoreceptors post injury. Together, these findings, do not demonstrate neuroprotective activity of BNN27 in experimentally-induced RD. Further studies are needed in order to elucidate the paradox/contradiction of these results and the mechanism of action of BNN27 in this model of photoreceptor cell damage.

Optical Biometry Derived Axial Length Measurements Following Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Macular Edema.

PURPOSE: To evaluate axial length (AL) alterations in patients with macular disease over the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: In this prospective, comparative study, 33 patients with macular edema underwent unilaterally intravitreal anti-VEGF therapy and were followed for two months; the contralateral eyes were considered as controls. Central retinal thickness (CRT) was measured with spectral-domain optical coherence tomography and AL with an IOL-Master optical biometer. RESULTS: CRT of the treated eyes decreased by 35.33 ± 65.59 µm (range, -222.00-67 µm), while AL increased by 0.008 ± 0.062 mm (range, -0.11-0.18 mm). CRT of the control group decreased by 9.82 ± 65.40 µm (range, -203-182 µm), and AL increased by 0.011 ± 0.129 mm (range, -0.20-0.67 mm). No significant correlation was detected between CRT and AL parameters (rhos=0.026, P=0.882). CONCLUSIONS: Anti-VEGF administration has no significant impact on optical biometry-derived AL measurements.

Combined transepithelial phototherapeutic keratectomy and conventional photorefractive keratectomy followed simultaneously by corneal crosslinking for keratoconus: Cretan protocol plus.

PURPOSE: To evaluate the visual, refractive, and topographic outcomes after combined transepithelial phototherapeutic keratectomy (PTK) and conventional photorefractive keratectomy (PRK) followed simultaneously by corneal crosslinking (CXL) for keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective case series. METHODS: Patients with progressive keratoconus had simultaneous conventional PRK followed by CXL; the corneal epithelium was removed using transepithelial PTK (Cretan protocol plus). The visual, refractive, and topographic outcomes and the endothelial cell density (ECD) were evaluated preoperatively and 1, 3, 6, and 12 months postoperatively. RESULTS: Forty-three patients (55 eyes) were enrolled. The mean uncorrected and corrected distance visual acuities improved significantly from 0.98 ± 0.63 (SD) logarithm of minimum angle of resolution (logMAR) and 0.20 ±â€¯0.23 logMAR preoperatively to 0.39 ±â€¯0.35 logMAR (P < .001) and 0.08 ±â€¯0.16 logMAR (P < .001) 12 months postoperatively, respectively. The mean spherical equivalent improved significantly from -4.67 ±â€¯4.00 diopters (D) preoperatively to -2.24 ±â€¯2.81 D (P < .001) at 12 months. The mean steep keratometry (K) and flat keratometry readings decreased significantly from 50.30 ±â€¯5.00 D and 45.62 ±â€¯3.10 D preoperatively to 46.27 ±â€¯3.90 D (P < .001) and 43.46 ±â€¯3.00 D (P < .001) 12 months postoperatively, respectively. No ECD alterations were observed throughout the follow-up (P > .05). CONCLUSION: Combined transepithelial PTK and conventional PRK followed simultaneously by CXL was effective in corneal stabilization and vision improvement in keratoconic patients.

Pharmacokinetics and efficacy of intraocular flurbiprofen.

PURPOSE: Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. METHODS: For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. RESULTS: No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. CONCLUSIONS: Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

Guidelines for the Management of Wet Age-Related Macular Degeneration: Recommendations from a Panel of Greek Experts.

PURPOSE: To propose guidelines for the management of patients with wet age-related macular degeneration (wAMD), taking into account the results of large multicenter studies and clinical experience of retina experts. METHOD: A team of retina experts developed a consensus paper after three consecutive meetings. The group was focused on guidelines to help clinical decision-making around the definition of successful treatment and the definition of non-response to therapy. RESULTS: Parameters suggestive of a successful response to treatments included: any gain in best corrected visual acuity (BCVA) or vision loss that is less than 5-10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, reduction of central retinal thickness, partial or complete absorption of subretinal fluid (SRF), reduction of intraretinal fluid, reduction of pigment epithelial detachment or restoration of the anatomy of outer retinal layers. Non-response to current treatment was considered in the case of loss of BCVA greater than 10 ETDRS letters, increased retinal edema or increase of SRF as evidenced by optical coherence tomography or new bleeding in biomicroscopy. CONCLUSION: The introduction of anti-VEGF agents revolutionized the treatment of wAMD. Given the complexity of the disease, the emerging new agents and the difference of cases recruited in clinical trials compared to those appearing in every-day practice, it is essential to individualize treatment options taking into account the results of clinical trials.

Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD.

Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

Intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery.

PURPOSE: To report two cases of chronic postoperative cystoid macular edema, resistant to topical therapy, treated with consecutive intravitreal injections of ketorolac tromethamine. METHODS: Four daily intravitreal injections of 500 µg/0.05 mL of ketorolac were given to each patient. Complete clinical examination and OCT were performed before every injection, 1, 2, 3 weeks, and 1, 3, and 6 months after the last injection. Fluorescein angiography was performed at baseline examination, 1, 3, and 6 months after the last injection. RESULTS: In both cases, the edema regressed and visual acuity increased. At 6 months after the last injection, the leakage was significantly reduced at the fluorescein angiography. DISCUSSION: Both cases responded favorably to the consecutive intravitreal administration of ketorolac tromethamine. The long-lasting remission of the macular edema in these chronic cases underlines the therapeutic potential of these agents when delivered intravitreally.

Effect of the Regenerative Agent Poly(Carboxymethylglucose Sulfate) on Corneal Wound Healing After Corneal Cross-Linking for Keratoconus.

PURPOSE: To evaluate the effect of a regenerative agent (RGTA) [Cacicol20-poly(carboxymethyl glucose sulfate); OTR3, Paris, France] on corneal reepithelialization and pain after corneal cross-linking (CXL) for keratoconus. METHODS: In this prospective comparative (contralateral) clinical study, patients with bilateral progressive keratoconus underwent CXL treatment. The corneal epithelium during CXL was removed using transepithelial phototherapeutic keratectomy (Cretan protocol). One eye of each patient was randomly instilled with an RGTA (Cacicol20) once a day (study group), whereas the fellow eye was instilled with artificial tears (control group). Patients were examined daily until complete reepithelialization. Postoperative examinations included slit-lamp biomicroscopy to assess the epithelial defect size and subjective evaluation of pain. RESULTS: The study enrolled 18 patients (36 eyes). The mean epithelial defect size for study and control groups was 19.6 ± 4.2 mm versus 21.5 ± 2.8 mm, respectively, at day 1 (P = 0.019) and 6.4 ± 3.4 mm versus 7.9 ± 4.3 mm, respectively, at day 2 (P = 0.014). At day 3 postoperatively, 61.1% of study eyes were fully reepithelialized, compared with 11.1% of control eyes (P = 0.002). CONCLUSIONS: RGTA (Cacicol20) instillation seems to result in faster corneal reepithelialization after CXL in this study. However, there was no significant effect in subjective pain/discomfort.