Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Faricimab Effectively Resolves Intraretinal Fluid and Preserves Vision in Refractory, Recalcitrant, and Nonresponsive Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the functional and anatomic outcomes of faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) who are unresponsive to other anti-vascular endothelial growth factor (VEGF) therapies. METHODS: A retrospective interventional study was conducted on patients with refractory nAMD who were initially treated with intravitreal bevacizumab, ranibizumab, or aflibercept. These patients were switched to monthly faricimab injections. The central subfield thickness (CST), intraretinal fluid (IRF) or subretinal fluid (SRF) height, and visual acuities were compared before and after faricimab treatment. RESULTS: A total of 13 eyes (eight right eyes and five left eyes) from 11 patients were followed for 10.4 ± 6.9 months after bevacizumab treatment and 40.3 ± 28.7 months after aflibercept treatment before switching to faricimab. The follow-up time for patients receiving a mean number of 3.7 ± 1.3 faricimab injections was 3.4 ± 1.2 months. The overall median CST was reduced by 18µm (p=0.001) from 342µm to 318µm, along with a reduction of 89µm (p=0.03) in IRF/SRF height from 97µm to 40µm. Following three consecutive injections, the CST showed a significant reduction of 21.5µm (p=0.004) from 344µm to 322.5µm, and IRF/SRF height was reduced by 89µm (p=0.03) from 104µm to 18.5µm. The intraretinal fluid size decreased and leakage stopped, as seen on fluorescein angiography. Visual acuity remained stable after switching to faricimab treatment (0.59 ± 0.45 logMAR vs 0.58 ± 0.45 logMAR, p=1). CONCLUSIONS: Faricimab has proven to be an effective treatment for nAMD patients resistant to other anti-VEGF agents. It demonstrates significant anatomical improvement and vision preservation in this challenging patient population.

Photodynamic Therapy-Induced Acute Exudative Maculopathy (PAEM): Prevalence, Impact and Management Strategies.

Photodynamic therapy (PDT) has a niche role in treating various choroidal pathologies. PDT-induced acute exudative maculopathy (PAEM) is an uncommon complication of PDT that results in exudative retinal detachment and mild to severe decrease in vision. Successful management strategies include observation, local or systemic corticosteroids, and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Most cases return to visual acuity near baseline. This review summarizes what is known about PAEM to date including etiology, prevalence, management strategies, and outcomes. We conclude that management of PAEM must take into consideration various patient-specific factors. Treatment with corticosteroids or anti-VEGF agents may expedite time to recovery, though lack of randomized controlled trials preclude firm conclusions regarding a standardized approach to managing this complication of PDT.

Baseline retinal thickness measurements with a novel integrated imaging system (concurrent optical coherence tomography and fundus photography) positively correlates with spectralis optical coherence tomography.

BACKGROUND: Traditionally fundus photographs and optical coherence tomography (OCT) are obtained separately during evaluation of retinal pathology. We describe a novel integrated imaging system (Monaco, Optos) that records both OCT as well as fundus photography concurrently. The present study aims to measure retinal thickness and compare it to OCT obtained with traditional spectral domain OCT in subjects without known retinal disease to establish normative data for clinical use. METHODS: In this cross sectional study, fundus photographs and OCT was obtained concurrently in 34 eyes in healthy patients without any known retinal disease with integrated imaging system. OCT with spectralis was also obtained at the same visit for comparison. All subjects underwent a complete ophthalmologic exam to ensure the absence of ocular pathology. OCT was performed by the same operator. Central subfield thickness (CST), central point thickness (CPT), and retinal thickness in nine central subfields were measured with both 1 instruments. Fundus photographs were obtained. Students t-test was used to determine statistical significance. RESULTS: The mean CST as measured with MIIS-SD OCT and Spectralis OCT was 300.53±22.81 µm and 265.18±17.33 µm (P<0.001) respectively. The Pearson's correlation coefficient, r value was 0.5285, P<0.0013. The mean CPT as measured with MIIS-SD OCT and Spectralis OCT was 268.55±20.70 and 230.67±17.75 µm (P<0.001) respectively. The r-value was 0.5697, P<0.0004. The mean difference between retinal thicknesses was 44.88 µm (range, 21-91 µm) in the eight ETDRS subfields, with r value 0.53, P<0.05, ranging from 0.51 to 0.60. Concurrently obtained ultrawide angle fundus photographs revealed (200°) clear media, normal disc, normal vasculature and normal periphery in all patients with excellent resolution. CONCLUSIONS: Retinal thickness measurements strongly correlated with those obtained by Spectralis. An increased measurement in thickness of 35.35 µm was noted in the central fovea. In addition, wide-angle fundus photography was successfully obtained in all subjects. Integrated system provides quality fundus photographs as well as OCT, obviates the need for two separate instruments and likely improves the clinic flow.

SUDDEN VISION LOSS FROM CENTRAL RETINAL ARTERY OCCLUSION AS A PRESENTING SYMPTOM OF MITRAL VALVE PAPILLARY FIBROELASTOMA.

PURPOSE: We describe a central retinal artery occlusion with cilioretinal sparing in a young male patient who was found to have mitral valve papillary fibroelastoma. METHODS: At the initial examination, a 33-year-old Hispanic man had visual acuity of 20/200 in his left eye, and 2 weeks later, visual acuity improved to 20/20. Diagnosis required transesophageal echocardiography to localize the lesion. RESULTS: Mitral valve papillary fibroelastoma involving the mitral valve was successfully treated with tumor resection. CONCLUSION: Routine echocardiography should be performed in all patients presenting with central retinal artery occlusion as it may diagnose treatable cardiogenic etiologies and present further potentially life-threatening embolic events.

Successful Management of Complex Rhegmatogenous Retinal Detachment in Congenital Glaucoma.

 Retinal detachment in congenital glaucoma is rare and often associated with a poor prognosis. In this report, we describe ocular manifestations of congenital glaucoma, pre- and post-operative ophthalmic findings, and overall anatomic and functional outcomes after successful rhegmatogenous retinal detachment repair along with a review of the literature. Rhegmatogenous retinal detachment in a 45-year-old monocular patient with congenital glaucoma was successfully repaired with small gauge pars plana vitrectomy, intra-operative perfluorocarbon use and 1,000 centistoke silicone oil tamponade. Best-corrected visual acuity improved from CF to 20/70; however, the post-operative course was complicated by hypotony-associated maculopathy after removal of silicone oil. Five thousand centistoke silicone oil was reinfused with good anatomic and functional outcomes. The functional outcome may ultimately be limited by pre-existing amblyopia and other ocular comorbidities.

Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments.

Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts.

The role of oral steroids in the treatment of photodynamic therapy-associated exudative maculopathy, a case report and review of the literature.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment of pachychoroid spectrum disease. PDT can cause a rare complication known as PDT-associated exudative maculopathy (PAEM). Treatments including intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications, local or systemic steroids, and observation have been attempted with variable success to address this complication. METHODS: A thorough literature review was performed using the PubMed database on search terms aimed at treatments of PAEM. These cases were compared with each other and a novel case of PAEM in polypoidal choroidal vasculopathy (PCV) treated with oral prednisone by the authors. RESULTS: Fifteen patients were compared; 11 were treated with anti-VEGF alone or in combination with intravitreal steroid and/or vitrectomy, one was treated with topical steroid, one was observed, one was treated with intravenous methylprednisolone, and one was treated with oral prednisone. The two cases treated with systemic steroids were given adjunctive sub-tenon's triamcinolone acetonide (STTA) after a favorable response was observed. Most cases had anatomic resolution of serous retinal detachment with stability of vision between 16 days and 2 months, with the most rapid resolution occurring in a patient with PCV treated with oral prednisone and STTA. CONCLUSIONS: Reported treatment of PAEM includes intravitreal anti-VEGF agents with or without local or systemic steroids. Oral steroids may be advantageous in cases where there is concern regarding the risk profile of periocular steroids, intravitreal steroids or anti-VEGF agents. However, data describing the various treatments of this rare complication is limited, precluding firm conclusions regarding relative safety and efficacy.

Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis.

Exudative age related macular degeneration (AMD) is related to active choroidal neovascularization (CNV) and formation of disciform scars. Vascular endothelial growth factor (VEGF) mediated choroidal vascular endothelial cell (CVECs) proliferation is characteristic of CNV. Intravitreal injections of bevacizumab, ranibizumab and aflibercept (anti-VEGF monoclonal antibodies) are used to treat exudative AMD. Pazopanib, a tyrosine kinase inhibitor, inhibits neovascularization through blockade of intracellular tyrosine kinase VEGF receptor and platelet-derived growth factor receptor. In this in vitro investigation, we evaluated the inhibitory consequences of escalating doses of pazopanib on proliferation of VEGF-enriched CVECs to establish a safe dosage range. VEGF (50 ng/mL) enriched CVECs were treated with escalating doses of pazopanib (10, 50,100 and 250 µM). Cell proliferation rates (WST-1 assay), cell viability (trypan blue exclusion assay), and reactive oxygen species (ROS) levels were measured at 48 hours (h), 72h and 1 week. Intracellular caspase 3 levels and morphological changes were recorded. VEGF enriched CVECs showed a significant decrease in cell proliferation rates after one week of treatment with increasing doses of pazopanib (10, 50,100 and 250 µM) treatment i.e. 87.8%, 43.0%, 38.1% and 9.3% compared to controls (p<0.001). Similarly, trypan blue exclusion assay revealed a decrease in cell viability as 81.8%, 81.0%, 53.4% and 8.7%, respectively (p<0.05). Further, pazopanib actively inhibited proliferation of VEGF-enriched CVECs, with 1.32, 1.92, 1.92 and 4.1-fold increase (p<0.01) in intracellular caspase 3 levels. VEGF-enriched CVECs treated with escalating doses of pazopanib decreased cell viability and increased caspase 3 levels in a time and dose dependent manner.

Endophthalmitis after dropless (Tri-Moxi injection) cataract surgery.

INTRODUCTION: A case of endophthalmitis after dropless cataract surgery with intravitreal Tri-Moxi associated with severe vision loss. CASE SUMMARY: An 82-year-old male developed severe vision loss in the left eye 24 days after dropless cataract surgery with intravitreal Tri-Moxi injection. Best corrected visual acuity was hand motion in the left eye. Intraocular pressure was 13, with inferior keratic precipitates, 4 + cell with 1 mm layered hypopyon, and a plaque on the posterior capsule that blocked direct exam of the posterior segment. Ultrasonography revealed extensive vitritis without retinal or choroidal detachments. CONCLUSION: Endophthalmitis resolved and vision improved after management with vitreous tap, intravitreal and fortified topical antibiotics, and subsequent prompt pars plana vitrectomy. Vitreous sample grew fluoroquinolone-resistant staphylococcus epidermidis.

Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial.

Importance: Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. Objective: To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. Design, Setting, and Participants: Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. Interventions: Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (≥ 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. Main Outcomes and Measures: The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. Results: Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208) in the aflibercept, laser photocoagulation, and observation groups, respectively (aflibercept vs laser photocoagulation risk difference, -2% [95% CI, -9% to 5%]; relative risk, 0.88 [95% CI, 0.57-1.35; P = .79]; aflibercept vs observation risk difference, -3% [95% CI, -11% to 4%]; relative risk, 0.83 [95% CI, 0.55-1.27; P = .79]; laser photocoagulation vs observation risk difference, -1% [95% CI, -9% to 6%]; relative risk, 0.95 [95% CI, 0.64-1.41; P = .79]). Antiplatelet Trialists' Collaboration vascular events occurred in 15 (7%), 13 (5%), and 8 (3%) participants in the aflibercept, laser photocoagulation, and observation groups. Conclusions and Relevance: Among eyes with CI-DME and good visual acuity, there was no significant difference in vision loss at 2 years whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. Observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. Trial Registration: ClinicalTrials.gov Identifier: NCT01909791.

Assistant Independent Self-retaining Truncated Gonioscopy Contact Lens for Minimally Invasive Glaucoma Surgery.

A new assistant independent self-retaining surgical goniolens provide panoramic view of angle during ocular surgery by means of new optical system that consists of 2 fused elements. First element comprises of a concave lens that mirror corneal curvature with 3 stabilizing feet for retention and stability on corneal surface during surgery. Second element comprise of a fused biconvex lens with prism that direct images of the angle through prism into surgical microscope. This surgical lens can be used for visualization of angle during all glaucoma procedures and especially helpful for performing minimally invasive glaucoma surgery.

EXTREME DIURNAL VARIATION OF CENTRAL MACULAR THICKNESS IN DIABETIC MACULAR EDEMA.

PURPOSE: Spectral domain optical coherence tomography is an established modality to quantify diabetic macular edema (DME). Change in central subfield thickness exceeding 3% to 6% in DME is likely to be significant. In this case of DME, we describe an extreme bilateral variation in central macular thickness on spectral domain optical coherence tomography over two consecutive days without any treatment. METHODS: The patient with DME and nonproliferative diabetic retinopathy underwent visual acuity testing, slit-lamp biomicroscopy, and dilated fundus examination. The patient also underwent spectral domain optical coherence tomography and digital fluorescence angiography. Findings are described in case report. RESULTS: There was an overnight decrease of central subfield thickness from 360 microns to 291 microns (69 [∼19%] microns) in the right eye and from 404 microns to 293 microns (111 [∼27%] microns) in the left eye. CONCLUSION: Extreme fluctuations in retinal thickness in central involving DME are unusual, and the exact mechanism of this fluctuation is poorly understood.

TEMPORAL THINNING IN SICKLE CELL RETINOPATHY IS ASSOCIATED WITH DIMINISHED PERFUSION ON OCTA AND DENSE SCOTOMA ON MICROPERIMETERY.

PURPOSE: To establish correlation between the structural compromise (capillary loss and hypoperfusion on optical coherence tomography [optical coherence tomography angiography]) with perimacular functional impairment noted on microperimetry. METHODS: Retrospective case series. Clinical records and multimodal imaging findings of patients presenting with sickle cell disease were reviewed. RESULTS: Three eyes of three patients (two men) were included in the study with a visual acuity of 20/20 and no sickle cell retinopathy. Images using optical coherence tomography angiography (AngioVue OCT angiography system; Optovue, Inc, Fremont, CA) were obtained along with spectral domain optical coherence tomography, fluorescein angiography, and microperimetry (MP-1). Spectral domain optical coherence tomography revealed selective loss of inner retinal layers with thinning of the retina. Optical coherence tomography angiography revealed compromise of both superficial and deep capillaries in the area of temporal thinning expressed on spectral domain optical coherence tomography. MP-1 demonstrated focal increase in threshold (decreased sensitivity) correlating with the perfusion defects on optical coherence tomography angiography. Fluorescein angiography did not show any substantial perfusion compromise. CONCLUSION: Optical coherence tomography angiography may reflect the extent of functional compromise even before it being evident on fluorescein angiography. The area vascular compromise was larger in the deep plexus compared with the superficial plexus. The area of complete loss of retinal sensitivity corresponds to loss of vasculature in both the superficial and deep plexuses, whereas the area of decreased sensitivities corresponds to compromise only in the deep plexus.

Loss of Angiotensin-Converting Enzyme 2 Exacerbates Diabetic Retinopathy by Promoting Bone Marrow Dysfunction.

Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis toward myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation. Migratory and proliferative dysfunction of these cells was corrected by exposure to angiotensin-1-7 (Ang-1-7), the protective peptide generated by ACE2. Over the duration of diabetes examined, ACE2 deficiency led to progressive reduction in electrical responses assessed by electroretinography and to increases in neural infarcts observed by fundus photography. Compared with Akita mice, ACE2-/y -Akita at 9-months of diabetes showed an increased number of acellular capillaries indicative of more severe diabetic retinopathy. In diabetic and control human subjects, CD34+ cells, a key bone marrow HS/PC population, were assessed for changes in mRNA levels for MAS, the receptor for Ang-1-7. Levels were highest in CD34+ cells from diabetics without retinopathy. Higher serum Ang-1-7 levels predicted protection from development of retinopathy in diabetics. Treatment with Ang-1-7 or alamandine restored the impaired migration function of CD34+ cells from subjects with retinopathy. These data support that activation of the protective RAS within HS/PCs may represents a therapeutic strategy for prevention of diabetic retinopathy. Stem Cells 2018;36:1430-1440.

The application of optical coherence tomography angiography in retinal diseases.

Optical coherence tomography angiography (OCTA) is a new, noninvasive imaging technique that generates real-time volumetric data on chorioretinal vasculature and its flow pattern. With the advent of high-speed optical coherence tomography, established enface chorioretinal segmentation, and efficient algorithms, OCTA generates images that resemble an angiogram. The principle of OCTA involves determining the change in backscattering between consecutive B-scans and then attributing the differences to the flow of erythrocytes through retinal blood vessels. OCTA has shown promise in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions. It quantifies vascular compromise reflecting the severity of diabetic retinopathy. OCTA detects the presence of choroidal neovascularization in exudative age-related macular degeneration and maps loss of choriocapillaris in nonexudative age-related macular degeneration. We describe principles of OCTA and findings in common and some uncommon retinal pathologies. Finally, we summarize its potential future applications. Its current limitations include a relatively small field of view, inability to show leakage, and a tendency for image artifacts. Further larger studies will define OCTAs utility in clinical settings and establish if the technology may offer its utility in decreasing morbidity through early detection and guide therapeutic interventions in retinal diseases.

Characterization of Vitreous and Aqueous Proteome in Humans With Proliferative Diabetic Retinopathy and Its Clinical Correlation.

AIMS: Proliferative diabetic retinopathy (PDR) is associated with microvascular complications that cause biochemical changes in the human retina and alter the proteome of vitreous humor and aqueous humor (AH). METHODS: Human vitreous humor and AH of PDR subjects were collected. Subjects who had surgery for epiretinal membrane or macular hole served as controls. Protein profiles were obtained and analyzed after running the samples on a liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: In vitreous humor, 16 unique proteins were noted in PDR patients, but not in controls. Those were associated mainly with coagulation, complement, and kallikrein-kinin systems. Under coagulation, fibrinogen and prothrombin proteins were more evident and may emphasize the importance of angiogenesis in the development of PDR. Vitreous proteins showed replicative presence in AH too. As for AH samples, we detected 10 proteins found in PDR patients, which were related to transport, coagulation, and inflammatory responses. CONCLUSIONS: We found 57 proteins in human vitreous and 39 proteins in AH. Identification of these proteins that are involved in various pathways will be helpful to understand diabetic retinopathy pathogenesis and to develop proteome as a biomarker for PDR.

Deep Capillary Macular Perfusion Indices Obtained with OCT Angiography Correlate with Degree of Nonproliferative Diabetic Retinopathy.

PURPOSE: To evaluate the integrity of macular and temporomacular vasculature in nonproliferative diabetic retinopathy (NPDR) with noninvasive optical coherence tomography angiography (OCTA) and correlate perfusion indices with degree of NPDR. METHODS: In this prospective observational cross-sectional study, 102 eyes with newly diagnosed NPDR (mild NPDR, 36; moderate NPDR, 21; severe NPDR, 13; NPDR with diabetic macular edema [DME], 32) underwent OCTA. Sixty eyes of normal subjects served as control. Degree of NPDR (based on Early Treatment Diabetic Retinopathy Study criteria) was confirmed with fluorescein angiography. Automated OCTA/split-spectrum amplitude decorrelation angiography software generated perfusion indices (vessel density and flow index) from images of the retina. The perfusion index of superficial and deep retinal plexuses was obtained in both perifoveal (central 1-3 mm) and parafoveal (3-6 mm) areas. RESULTS: Deep plexus parafoveal vessel density was 25.23% (±6.1) in mild NPDR, 20.16% (±6.16) in moderate NPDR, 11.16% (±4.16) in severe NPDR, and 17.91% (±4.42) in NPDR + DME compared to normal subjects (36.93% [±8.1]; (p<0.01). Spearman correlation coefficient (rs) between vessel density and level of NPDR severity in the parafoveal region showed inverse correlation for both superficial (rs -0.87; p = 0.083) and deep (rs -0.96; p = 0.017) plexus. Similarly, when vessel density of the perifoveal region was compared with level of NPDR severity, inverse correlation was noted in both superficial (rs -0.85; p = 0.08) and deep (rs -0.98; p = 0.011) plexus. CONCLUSIONS: Optical coherence tomography angiography clearly delineated the retinal microcirculation and allowed quantification of vascular perfusion of each layer. As diabetic retinopathy progressed, a decrease in perfusion index is more pronounced in the deep retinal plexus and precedes changes in superficial plexus.

Inhibition of proliferation of retinal vascular endothelial cells more effectively than choroidal vascular endothelial cell proliferation by bevacizumab.

AIM: To evaluate the differential inhibitory effects of bevacizumab on cell proliferation of vascular endothelial growth factor (VEGF)-stimulated choroidal vascular endothelial cells (CVECs) and retinal vascular endothelial cells (RVECs) in vitro. METHODS: VEGF (400 ng/mL) enriched CVECs and RVECs were treated with escalating doses of bevacizumab (0.1, 0.5, 1, 1.5 and 2 mg/mL). Cell proliferation changes were analyzed with WST-1 assay and trypan blue exclusion assay at 48, 72h and 1wk. Morphological changes were recorded with bright field microscopy. RESULTS: VEGF enriched RVECs showed significantly more decline of cell viability than CVECs after bevacizumab treatment. One week after treatment, RVEC cell proliferation decreased by 29.7%, 37.5%, 52.8%, 35.9% and 45.6% at 0.1, 0.5, 1.0, 1.5 and 2 mg/mL bevacizumab respectively compared to CVEC proliferation decrease of 4.1%, 7.7%, 2.4%, 4.1% and 17.7% (P<0.05) by WST-1 assay. Trypan blue exclusion assay also revealed similar decrease in RVEC proliferation of 20%, 60%, 73.3%, 80% and 93.3% compared to CVEC proliferation decrease of 4%, 12%, 22.9%, 16.7% and 22.2% respectively (P<0.05). The maximum differential effect between the two cell types was observed at bevacizumab doses of 1.0 and 1.5 mg/mL at all time points. RVECs were 22 fold more sensitive (P<0.01) compared to CVECs (52.8% vs 2.4%) at concentration of 1.0 mg/mL, and 8.7 fold more at 1.5 mg/mL (35.9% vs 4.1%) 1wk after treatment (P<0.05 respectively). CONCLUSION: VEGF-enriched RVECs are more susceptible to bevacizumab inhibition than CVECs at clinically used dosage of 1.25 mg and this differential sensitivity between two cell types should be taken into consideration in dosage selection.

Sirtuins Expression and Their Role in Retinal Diseases.

Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confer protection against oxidative stress and retinal degeneration. In mammals, the sirtuin (SIRT) family consists of seven proteins (SIRT1-SIRT7). These vary in tissue specificity, subcellular localization, and enzymatic activity and targets. In this review, we present the current knowledge of the sirtuin family and discuss their structure, cellular location, and biological function with a primary focus on their role in different neuroophthalmic diseases including glaucoma, optic neuritis, and age-related macular degeneration. The potential role of certain therapeutic targets is also described.