Decrease In Retinal Thickness Research Articles

Parapapillary Choroidal Microvasculature Dropout Is Associated With the Decrease in Retinal Nerve Fiber Layer Thickness: A Prospective Study.

To explore the correlation between longitudinal changes of peripapillary retinal nerve fiber layer (RNFL) thickness and the presence of parapapillary choroidal microvasculature dropout (MvD). This is a longitudinal cohort study. All patients with normal-tension glaucoma (NTG) were recruited from the Wenzhou Glaucoma Progression Study. The presence of MvD was determined using optical coherence tomography (OCT) angiography and the RNFL thickness was evaluated by spectral-domain OCT. All assessments were performed both at baseline and at every 3-month follow-up for at least 18 months. Seventy-one eyes were included. The presence of MvD was observed in 23 NTG eyes (32.4%). Eyes with MvD had a thinner RNFL (68.8 ± 9.6 vs. 76.2 ± 16.7 μm, P = 0.016) and a faster rate of RNFL loss (-1.2 ± 1.5 vs. -0.4 ± 1.4 μm/y, P = 0.036) compared with those without MvD. In a univariate analysis of rates of RNFL loss, the presence of MvD at baseline (β = -0.83 ± 0.38, P = 0.033) was significantly associated with progressive RNFL loss. After adjusting for age, female sex, mean follow-up IOP, axial length, central corneal thickness, and mean deviation, the presence of MvD at baseline (β = -0.85 ± 0.41, P = 0.041) was significantly associated with faster rates of RNFL loss in the multivariate analysis. There is a significant correlation between the presence of MvD and decrease in RNFL thickness in NTG patients. Our study further supported that the presence of MvD is a predictor of longitudinal RNFL damage in glaucoma.

Injectable 0.19-mg fluocinolone acetonide intravitreal implant for the treatment of non-infectious uveitic macular edema

BackgroundA retrospective observational clinical study to evaluate the safety and effectiveness of the injectable 0.19-mg fluocinolone acetonide intravitreal implant (ILUVIEN) in the treatment of non-infectious uveitic macular edema.ResultsData are presented from eight patients (11 eyes) with non-infectious uveitic macular edema who were treated with a 0.19-mg fluocinolone acetonide implant. Nine out of 11 eyes were pseudophakic prior to implantation of fluocinolone acetonide implant, and both phakic eyes required cataract surgery during the follow-up period (the median follow-up was 19 months; range, 8–42 months). Effectiveness and safety were assessed from changes in central retinal thickness (measured using spectral domain optical coherence tomography), corrected distance visual acuity, uveitic activity, and intraocular pressure.The main outcome measures were changes in central retinal thickness, corrected distance visual acuity, uveitic activity, and intraocular pressure. In 11/11 eyes, central retinal thickness improved between months 1 and 3. The mean maximum decrease of central retinal thickness throughout the follow-up period was 168 ± 202 μm (± standard deviation). Nine out of 11 eyes showed an improvement in corrected distance visual acuity (between + 1 and + 8 lines), and 2/11 eyes lost corrected distance visual acuity (− 1 and − 3 lines, respectively). Nine out of 11 eyes presented with inactive inflammation during the follow-up period, and in 1/11 eyes, there was a relapse at month 42. Four out of 11 eyes presented with a relapse of macular edema between months 3 and 8. The mean increase in intraocular pressure was 2.1 ± 4.7 mmHg. Nine eyes were pseudophakic prior to implantation of the injectable fluocinolone acetonide intravitreal implant. Both phakic patients developed a cataract that was treated with cataract surgery in the follow-up period.ConclusionsIn this small case series with long-term follow-up, treatment of non-infectious uveitic macular edema with the injectable fluocinolone acetonide implant was associated with improved central retinal thickness and corrected distance visual acuity and a manageable safety profile. The advantage of this device is the long-term drug release and the fact that it can be injected into the vitreous as a minor surgical procedure, which is in contrast to other treatment options.

Hyperreflective foci on optical coherence tomography associate with treatment outcome for anti-VEGF in patients with diabetic macular edema.

PurposeTo investigate the relationship between baseline number of hyperreflective foci (HF) on spectral domain optical coherence tomography (SD-OCT) in patients with diabetic macular edema (DME), as well as the dynamics of HF during treatment with anti-vascular endothelial growth factor (VEGF), and treatment response.MethodsWe evaluated patients diagnosed with DME scheduled for treatment with intravitreal bevacizumab. Eyes were classified as adequate or insufficient treatment responders based on logMAR visual acuity improvement and central retinal thickness (CRT) decrease after three consecutive injections. Associations between number of HF at baseline and treatment response, the change in HF over the course of treatment, and the distribution of HF within the retinal layers were evaluated.ResultsIn 54 eyes of 41 patients, mean number of HF and CRT decreased after intravitreal treatment with bevacizumab (p = 0.002 and p<0.001 respectively). Decrease in CRT after 3 months was independently associated with a higher number of HF at baseline (estimated effect -2.61, 95% CI [-4.42–-0.31], p = 0.006). Eyes with adequate treatment response presented with more HF at baseline (OR 1.106, 95% CI [1.012–1.210], p = 0.030) than eyes with insufficient treatment response. Most HF were located within the inner retinal layers, and decrease of HF was mostly due to a decrease of inner retinal HF.ConclusionsIn patients with DME treated with anti-VEGF, higher baseline numbers of HF have predictive value for treatment response in terms of visual acuity improvement and CRT decrease after 3 months. In addition, HF were responsive to anti-VEGF therapy.

Baseline diagnostics and initial treatment decision for anti-vascular endothelial growth factor treatment in retinal diseases : Comparison between results by study physician and reading centers (ORCA/OCEAN study)

The ORCA module of the non-interventional OCEAN study investigated the use of retinal imaging diagnostics in the clinical treatment of patients undergoing vascular endothelial growth factor (VEGF) inhibitor treatment as part of routine clinical care. This article analyzes the agreement between the diagnosis documented by the treating ophthalmologist and the evaluation of reading centers at baseline as well as the effect on the response to treatment during the course. Atotal of 396 patients (age 75.4years) were enrolled in which ranibizumab treatment was indicated by the treating ophthalmologist due to either diabetic macular edema (DME), neovascular age-related macular degeneration (nvAMD) or retinal venous occlusion (RVO). Over aperiod of 24months, patient and examination data, treatments and interpretation of retinal imaging data by the treating ophthalmologist were systematically recorded. Furthermore, retinal imaging data were also evaluated by three reading centers. In 338 out of 396 (85.4%) study eyes, the baseline diagnosis of the treating ophthalmologist was confirmed by the reading centers (DME 87.5%, nvAMD 82.3%, RVO 94.9%). In 17 of the remaining 58eyes with a discrepant diagnosis, there was at least a consensus with respect to the indications for VEGF inhibitor therapy. The differential diagnoses included avariety of different retinal diseases. During follow-up of up to 3 months, eyes with aconsistent diagnosis showed aclear increase in visual acuity (6.4 versus 2.7letters, p = 0.05) and greater decrease in central retinal thickness (-112.3 versus -24.4 μm, p < 0.0001). The initial treatment decision for anti-VEGF therapy with consideration of the differential diagnoses can be challenging. Accurate evaluation of the clinical and imaging findings along with appropriate expertise appear to be important. The observation of superior initial response in eyes with aconsensus of the diagnosis at baseline underlines the relevance of an adequate initial assessment for asuccessful treatment outcome.

ARCUATE NERVE FIBER LAYER CHANGES AFTER INTERNAL LIMITING MEMBRANE PEELING IN IDIOPATHIC EPIRETINAL MEMBRANE.

To analyze the relationship between swelling of the arcuate nerve fiber layer (SANFL) and long-term decrease of retinal nerve fiber layer thickness after internal limiting membrane peeling for idiopathic epiretinal membrane, and to investigate if SANFL is related to a mechanical surgical damage. Prospective, interventional consecutive case series of 46 eyes that underwent combined epiretinal membrane/internal limiting membrane peeling for idiopathic epiretinal membrane. Infrared, blue autofluorescence, color fundus imaging and measurement of retinal nerve fiber layer thickness in six peripapillary sectors by spectral-domain optical coherence tomography were performed preoperatively and at 2 weeks, 1, 3, 6, and 12 months after surgery. The presence of SANFL was checked postoperatively on infrared and blue autofluorescence fundus imaging, and the extent of each SANFL was measured on infrared fundus images. Areas of SANFL were identified in 39 eyes (84.8%) at 2-week follow-up. Retinal nerve fiber layer thickness significantly decreased in the temporal sectors at 1, 6, and 12 months (P < 0.0001). The linear extent of SANFL was significantly correlated with the percentage of reduction in retinal nerve fiber layer thickness in the temporal (R = 0.45; P < 0.0001) and infero-temporal (R = 0.23; P = 0.0008) sectors at 12 months of follow-up. Correspondence between sites of surgical grasping and the points of origin of SANFL was demonstrated on blue autofluorescence fundus images superimposed on intraoperative surgical frames. Early postoperative SANFL is correlated with late focal retinal nerve fiber layer thinning in the temporal sectors. Intraoperative surgical grasping seems to be a leading factor for the onset of SANFL.

Choroidal thickness changes stratified by outcome in real-world treatment of diabetic macular edema.

The aim of this study was to evaluate subfoveal choroidal thickness (SFCT) as a marker of outcome in real-world treatment of diabetic macular edema (DME) and to correlate it with choroidal thicknesses (CT) collected around the fovea. Prospective interventional case series included a total of 126 eyes from 126 patients with recently diagnosed DME treated with a 3-monthly loading dose of ranibizumab or aflibercept and PRN thereafter until 24months (M). CT was manually measured in the central 3500μm area, subfoveally (SFCT), at 1750μm right and left from the center in the horizontal plane and at 1750μm up and down from the center in the vertical plane, by OCT. Anatomic (10% decrease in central retinal thickness) and functional (gain ≥ 5 letters) responses were assessed using univariate and multivariate analyses. The areas under ROC curves were used to assess whether baseline SFCT was a predictor of outcome. CT significantly decreased in all follow-ups (3months after the 3 injections' loading dose (3M), 6months (6M), 12months (12M), 18months (18M), 24months (24M)). SFCT and other CT parameters are correlated. SFCT decrease from baseline was related with treatment (p = 0.003 to p < 0.001) but not with anatomic (3M, p = 0.858; 6M p = 0.762) or functional response (3M, p = 0.746; 6M, p = 0.156). SFCT was not found to be predictive of anatomic (AUC = 0.575, p = 0.172) or functional (AUC = 0.515, p = 0.779) outcome. SFCT is a reliable marker of choroidal thickness. Baseline SFCT decreased with anti-VEGF treatment but did not predict DME outcome.

Retinal dysfunction parallels morphologic alterations and precede clinically detectable vascular alterations in Meriones shawi, a model of type 2 diabetes

Diabetic retinopathy is a major cause of reduced visual acuity and acquired blindness. The aim of this work was to analyze functional and vascular changes in diabetic Meriones shawi (M.sh) an animal model of metabolic syndrome and type 2 diabetes. The animals were divided into four groups. Two groups were fed a high fat diet (HFD) for 3 and 7 months, two other groups served as age-matched controls. Retinal function was assessed using full field electroretinogram (Ff-ERG). Retinal thickness and vasculature were examined by optical coherence tomography, eye fundus and fluorescein angiography. Immunohistochemistry was used to examine key proteins of glutamate metabolism and synaptic transmission. Diabetic animals exhibited significantly delayed scotopic and photopic ERG responses and decreases in scotopic and photopic a- and b-wave amplitudes at both time points. Furthermore, a decrease of the amplitude of the flicker response and variable changes in the scotopic and photopic oscillatory potentials was reported. A significant decrease in retinal thickness was observed. No evident change in the visual streak area and no sign of vascular abnormality was present; however, some exudates in the periphery were visible in 7 months diabetic animals. Imunohistochemistry detected a decrease in the expression of glutamate synthetase, vesicular glutamate transporter 1 and synaptophysin proteins. Results indicate that a significant retinal dysfunction was present in the HFD induced diabetes involving both rod and cone pathways and this dysfunction correlate well with the morphological abnormalities reported previously. Furthermore, neurodegeneration and abnormalities in retinal function occur before vascular alterations would be detectable in diabetic M.sh.

Antarctica eye study: a prospective study of the effects of overwintering on ocular parameters and visual function

BackgroundIn 2013 five polar explorers attempted to complete the first Trans-Antarctic Winter Traverse (TAWT). This study presents the ophthalmological findings for this group, who overwintered in Antarctica as part of the White Mars Human Science Protocol. Antarctic crews are exposed to extreme cold, chronic hypoxia and altered day-night cycles. Previous studies of Antarctic explorers have focused on the prolonged effect of ultraviolet radiation including the development of ultraviolet keratitis and accelerated cataract formation. This is the first study of its kind to investigate the effect of overwintering in Antarctica on the human eye.MethodsPre and post-expedition clinical observations were made including visual acuity, contrast sensitivity, colour vision, auto-refraction, subjective refraction, retinal examination, retinal autofluoresence and retinal thickness, which were graded for comparison. During the expedition additional observations were made on a monthly basis including LogMAR visual acuity, autorefraction and intraocular pressure.ResultsNo significant differences between pre and post-expedition observations were found, including visual acuity, contrast sensitivity, colour vision, refraction, visual fields, intraocular pressure and retinal examination. There was a small but statistically significant decrease in retinal thickness across all regions of the retina, except for the macular and fovea, in all explorers. Intra-expedition observations remained within normal limits.ConclusionReassuringly, the human eye remains largely unchanged by exposure to the extreme conditions encountered during the Antarctic winter, however, further research is needed to investigate changes in retinal thickness. This may have implications for scientists who spend prolonged periods of time in the polar regions, as well as those who have prolonged exposure to the extreme cold or chronic hypoxia in other settings.

Association of Retinal Neurodegeneration on Optical Coherence Tomography With Dementia

Retinal structures may serve as a biomarker for dementia, but longitudinal studies examining this link are lacking. To investigate the association of inner retinal layer thickness with prevalent and incident dementia in a general population of Dutch adults. From September 2007 to June 2012, participants from the prospective population-based Rotterdam Study who were 45 years and older and had gradable retinal optical coherence tomography images and at baseline were free from stroke, Parkinson disease, multiple sclerosis, glaucoma, macular degeneration, retinopathy, myopia, hyperopia, and optic disc pathology were included. They were followed up until January 1, 2015, for the onset of dementia. Inner retinal layer thicknesses (ie, retinal nerve fiber layer [RNFL]) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses measured on optical coherence tomography images. Odds ratios and hazard ratios for incident dementia per SD decrease in retinal layer thickness adjusted for age, sex, education, and cardiovascular risk factors. Of 5065 individuals eligible for optical coherence tomography scanning, 3289 (64.9%) (mean [SD] age 68.9 [9.9] years, 1879 [57%] women) were included in the analysis. Of these 3289 individuals, 41 (1.2%) already had dementia. Thinner GC-IPL was associated with prevalent dementia (odds ratio per SD decrease in GC-IPL, 1.37 [95% CI, 0.99-1.90]). No association was found of RNFL with prevalent dementia. During 14 674 person-years of follow-up (mean [SD], 4.5 [1.6] years), 86 individuals (2.6%) developed dementia of whom 68 (2.1%) had Alzheimer disease. Thinner RNFL at baseline was associated with an increased risk of developing dementia (hazard ratio per SD decrease in RNFL, 1.44 [95% CI, 1.19-1.75]), which was similar for Alzheimer disease (hazard ratio, 1.43 [95% CI, 1.15-1.78]). No association was found between GC-IPL thickness and incident dementia (hazard ratio, 1.13 [95% CI, 0.90-1.43]). Thinner RNFL is associated with an increased risk of dementia, including Alzheimer disease, suggesting that retinal neurodegeneration may serve as a preclinical biomarker for dementia.

Characteristics of patients with neovascular age-related macular degeneration who are non-responders to intravitreal aflibercept

PurposeTo investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD).DesignRetrospective, interventional, consecutive case series.MethodsThree hundred and sixty-five eyes of...

OPTICAL COHERENCE TOMOGRAPHY BASELINE PREDICTORS FOR INITIAL BEST-CORRECTED VISUAL ACUITY RESPONSE TO INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN EYES WITH DIABETIC MACULAR EDEMA: The CHARTRES Study.

To identify baseline optical coherence tomography morphologic characteristics predicting the visual response to anti-vascular endothelial growth factor therapy in diabetic macular edema. Sixty-seven patients with diabetic macular edema completed a prospective, observational study (NCT01947881-CHARTRES). All patients received monthly intravitreal injections of Lucentis for 3 months followed by PRN treatment and underwent best-corrected visual acuity measurements and spectral domain optical coherence tomography at Baseline, Months 1, 2, 3, and 6. Visual treatment response was characterized as good (≥10 letters), moderate (5-10 letters), and poor (<5 or letters loss). Spectral domain optical coherence tomography images were graded before and after treatment by a certified Reading Center. One month after loading dose, 26 patients (38.80%) were identified as good responders, 19 (28.35%) as Moderate and 22 (32.83%) as poor responders. There were no significant best-corrected visual acuity and central retinal thickness differences at baseline (P = 0.176; P = 0.573, respectively). Ellipsoid zone disruption and disorganization of retinal inner layers were good predictors for treatment response, representing a significant risk for poor visual recovery to anti-vascular endothelial growth factor therapy (odds ratio = 10.96; P < 0.001 for ellipsoid zone disruption and odds ratio = 7.05; P = 0.034 for disorganization of retinal inner layers). Damage of ellipsoid zone, higher values of disorganization of retinal inner layers, and central retinal thickness decrease are good predictors of best-corrected visual acuity response to anti-vascular endothelial growth factor therapy.

Retinal thickness correlates with parietal cortical atrophy in early-onset Alzheimer's disease and controls

IntroductionThe retina may reflect Alzheimer's disease (AD) neuropathological changes and is easily visualized with optical coherence tomography (OCT). Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls. MethodsWe measured macular thickness and peripapillary retinal nerve fiber layer thickness with OCT in 15 EOAD patients and 15 controls and correlated retinal thickness to visual rating scores for atrophy on magnetic resonance imaging. ResultsTotal macular thickness correlated to parietal cortical atrophy in both groups (Spearman ρ −0.603, P = .001). Macular and peripapillary retinal nerve fiber layer thicknesses were not significantly decreased in EOAD compared to controls. DiscussionRetinal thickness does not discriminate EOAD from controls but is correlated to parietal cortical atrophy in both groups. These findings may suggest reflection of cerebral cortical changes in the retina, independent of amyloid.

PROSPECTIVE EVALUATION OF A SUSTAINED-RELEASE DEXAMETHASONE INTRAVITREAL IMPLANT FOR CYSTOID MACULAR EDEMA IN QUIESCENT UVEITIS.

To investigate dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc) in the treatment of uveitic cystoid macular edema that had persisted in the absence of intraocular inflammation. In this prospective interventional case series, 10 patients with uveitic cystoid macular edema and quiescent uveitis were treated with dexamethasone intravitreal implant at baseline and evaluated monthly for one year. Patients were retreated whenever cystoid macular edema recurred. The primary outcome measure was best-corrected visual acuity (BCVA) at day 90. At day 90, mean improvement from baseline BCVA was 14.4 letters (P = 0.0003), 70% of patients had a ≥10 letter BCVA improvement, 50% of patients had a ≥15 letter BCVA improvement, and the mean decrease from baseline central subfield retinal thickness was 140 μm (P = 0.008). Improvements were maintained through day 360 with retreatment as needed. At day 360, mean improvement in BCVA was 16.5 letters (P = 0.006) and the mean decrease in central subfield retinal thickness was 158 μm (P = 0.002). One patient experienced intraocular pressure >25 mmHg (managed with topical medication). Two phakic patients (2/8; 25%) had worsening of lens opacity requiring cataract extraction. Dexamethasone intravitreal implant may be an effective treatment for patients with persistent cystoid macular edema in quiescent uveitis.

Study of retinal neurodegeneration and maculopathy in diabetic Meriones shawi: A particular animal model with human-like macula.

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.

Do areas of retinal ganglion cell degeneration coincide with areas of decreased representation in V1 following stroke?

Stroke in the territory of the posterior cerebral artery leads to cortical blindness in a hemifield or quadrant of the contralesional visual field. While about 50% of patients experience some degree of visual recovery within the first 6 months post-stroke, only 12.5% experience complete recovery (Tiel K., Kolmel, 1990). One limiting factor that may prevent further visual recovery is trans-synaptic retrograde degeneration of retinal ganglion cells, which has been observed in stroke patients starting as early as 3 months after stroke (Jindahra, Petrie, & Plant, 2009, 2012; Park, Park, Cho, & Park, 2013; Tanito & Ohira, 2013; Yamahachi, Marik, McManus, Denk, & Gilbert, 2009). Retinal ganglion cell thickness is easily measured in the clinic with optical coherence tomography, a technique that generates a 3-D image of the retina from which the thickness of the retinal ganglion cell complex can be measured. The visual cortex is organized in a retinotopic manner that can be measured with fMRI by presenting visual stimuli in various locations in the participant's visual field and then determining the stimulus location for which each voxel maximally responds (Sereno et al., 1995). Here we test the hypothesis that chronic stroke patients exhibit a homonymous decrease in retinal ganglion cell thickness specifically for visual locations with poor representation in V1. This research has implications for timely rehabilitative treatment because once the retina degenerates, visual recovery in that retinotopic location is impossible. Furthermore, this research may highlight the need for novel treatment strategies that prevent retinal ganglion cell degeneration in order to prolong the window of effective rehabilitation.

Age-related macular degeneration: is polypoidal choroidal vasculopathy recognized and treated?

ObjectiveTo assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). DesignRetrospective chart review. Participants154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. MethodsAll newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. Results10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese (p = 0.004) and Caucasian patients (p = 0.03), were more likely to use photodynamic therapy (PDT) (p < 0.01), and had significantly greater central retinal thickness decrease (p < 0.001). ConclusionOur study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.

Effect of intravitreal aflibercept on recalcitrant diabetic macular edema

Background Despite anti-VEGF therapy, some patients develop chronic diabetic macular edema. The objective of this study was to evaluate anatomic and visual outcomes of switching patients with chronic DME from intravitreal bevacizumab or ranibizumab to intravitreal aflibercept injection.MethodsIn this retrospective observational case series, 11 eyes with recalcitrant diabetic macular edema (DME) were evaluated 6 months prior to and 6 months following initial intravitreal aflibercept injection (IAI). Recalcitrant DME was defined as having a thickened retina (≥350 μm) on spectral domain optical coherence tomography (SD-OCT) with persistent cystic changes (less than a 15% reduction in central retinal thickness) over 6 months prior to intravitreal aflibercept switch despite aggressive treatment for DME during this time.ResultsOne hundred and forty-seven patients in total were treated with IAI during this time, and of these, 31 patients were treated with IAI for DME. 18 eyes had less than 4 treatments within the 6 months prior to switch to IAI, 6 patients had a central retinal thickness (CRT) on SD-OCT of less than 350 μm at time of switch to IAI, and 2 patients had a greater than 15% decline in CRT on SD-OCT over the 6 months prior to switch to IAI. A total of 11 patients were included in the study. Over the 6 months prior to switch, the mean change in central retinal thickness was +18.6% and over the 6 months following switch to aflibercept the mean change in central retinal thickness was −27.1%. Switching to a regimen of at least 3 intravitreal aflibercept injections over 6 months resulted in some anatomic improvement and improvement or stabilization of Snellen visual acuity in all eligible patients.ConclusionsIn patients with recalcitrant diabetic macular edema, switching to intravitreal aflibercept resulted in improved a 25% or more decrease in central retinal thickness in 81% (9/11) patients at 6-month follow-up. Sixty-three percent (7/11) had improvement in Snellen visual acuity after switching to intravitreal aflibercept injection, suggesting some reversibility of functional damage.

Aqueous cytokine levels are associated with reduced macular thickness after intravitreal ranibizumab for diabetic macular edema.

PurposeIt is controversial whether the administration of anti-vascular endothelial growth factor drugs for diabetic macular edema (DME) affects intraocular inflammatory cytokines. In this study, we measured cytokine concentration in aqueous humor before and after intravitreal injection of ranibizumab (IVR). The aim was to determine changes in cytokine concentration and their effects on DME reduction.MethodsTwelve patients (13 eyes) with DME received two IVR (0.5 mg) with a 1 month interval, and a total of 26 aqueous humor samples were obtained. Macular thickness was measured with an optical coherence tomography (OCT) using thickness-map mode with an Early Treatment Diabetic Retinopathy Study (ETDRS) 9-zone grid that was divided into two zones: a central circle with a diameter of 1 mm (zone1); and an outer circle with a diameter of 6 mm (zone2).ResultsThe concentration of eotaxin-1 in aqueous humor samples decreased significantly after IVR. Baseline cytokine concentration was associated with IVR-induced DME reduction. In zone1, higher baseline concentration of interferon-induced protein (IP)-10, and in zone 2, higher baseline concentration of granulocyte-macrophage colony-stimulating factor, IP-10, and tumor necrosis factor (TNF) α; and lower baseline concentration of eotaxin-1, interleukin (IL)-5, and IL-8 were associated with improved DME. Cytokine changes were associated with IVR-induced DME reduction. In zone1, lower concentration of IP-10 compared to baseline or higher concentration of macrophage inflammatory protein (MIP) -α, and in zone 2, lower concentration of IL-5 compared to baseline, IL-8, and IP-10 or higher concentration of eotaxin-1 and MIP-1β were associated with improved DME.ConclusionsThese findings suggest that ranibizumab affects the concentration of cytokines in aqueous humor. Various cytokines contribute to a decrease in retinal thickness, both in the center of the macula and in a larger area of the retina.

The Protective Effects of αB-Crystallin on Ischemia-Reperfusion Injury in the Rat Retina.

To investigate whether αB-crystallin protects against acute retinal ischemic reperfusion injury (I/R) and elucidate the potential antioxidant mechanisms. Retinal I/R injury was made by elevating the intraocular pressure (IOP) 110 mmHg for 60 min, and αB-crystallin (1 × 10−5 g/L) or vehicle solution was administered intravitreously immediately after I/R injury. The animal was sacrificed 24 h, 1 w, and 1 m after the I/R injury. The retina damage was detected by hematoxylin and eosin (HE) staining and electroretinography (ERG). The level of malondialdehyde (MDA), nitric oxide (NO), and the total superoxide dismutase (T-SOD) was determined. An immunohistochemical study was performed to detect the activation of inducible nitric oxide synthase (iNOS) and NF- (nuclear factor-) kappaB (NF-κB) p65. The decrease of retinal thickness and the number of retinal ganglion cells (RGCs) can be suppressed by αB-crystallin. And the amplitudes of a- and b-wave were remarkably greater without αB-crystallin. Similarly, αB-crystallin also significantly decreased the level of MDA and NO and enhanced the activities of T-SOD. The positive expression of iNOS and NF-kappaB p65 was obviously reduced while treated with αB-crystallin. αB-crystallin can inhibit the expression of NF-κB and its antioxidative effect to protect the retina from I/R injury.

Depletion of the Third Complement Component Ameliorates Age-Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model.

The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress-, apoptosis-, and autophagy-related proteins were assessed in retinas of 12-month-old C3-deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age-dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl-1/Bak dimer, (3) lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase-3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age-related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.