Subthreshold micropulse laser combined with anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of subthreshold micropulse laser (SML) in addition to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were systematically searched for studies that compared anti-VEGF with SML and anti-VEGF monotherapy for DME. Outcome measures were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the number of anti-VEGF injections. RESULTS: Eight studies including 493 eyes were selected. Four studies were randomized controlled, and the other four were retrospective. Meta-analysis showed that there was no significant difference in BCVA (mean difference [MD] -0.04; 95%CI -0.09 to 0.01 logMAR; P = 0.13;). CMT was thinner in the group of anti-VEGF with SML (MD -11.08; 95%CI -21.04 to -1.12 µm; P = 0.03); however, it was due to a single study that weighed higher, and the sensitivity and subcategory analyses did not support the finding. The number of anti-VEGF injections was significantly decreased in the group of anti-VEGF with SML (MD -2.22; 95%CI -3.02 to -1.42; P < 0.0001). CONCLUSION: Current evidence indicates that adding SML to anti-VEGF therapy could significantly reduce the number of anti-VEGF injections compared to anti-VEGF monotherapy, while achieve similar BCVA and CMT.

Mitochondrial glutathione peroxidase 4 is indispensable for photoreceptor development and survival in mice.

Glutathione peroxidase 4 (GPx4) is known for its unique function in the direct detoxification of lipid peroxides in the cell membrane and as a key regulator of ferroptosis, a form of lipid peroxidation-induced nonapoptotic cell death. However, the cytosolic isoform of GPx4 is considered to play a major role in inhibiting ferroptosis in somatic cells, whereas the roles of the mitochondrial isoform of GPx4 (mGPx4) in cell survival are not yet clear. In the present study, we found that mGPx4 KO mice exhibit a cone-rod dystrophy-like phenotype in which loss of cone photoreceptors precedes loss of rod photoreceptors. Specifically, in mGPx4 KO mice, cone photoreceptors disappeared prior to their maturation, whereas rod photoreceptors persisted through maturation but gradually degenerated afterward. Mechanistically, we demonstrated that vitamin E supplementation significantly ameliorated photoreceptor loss in these mice. Furthermore, LC-MS showed a significant increase in peroxidized phosphatidylethanolamine esterified with docosahexaenoic acid in the retina of mGPx4 KO mice. We also observed shrunken and uniformly condensed nuclei as well as caspase-3 activation in mGPx4 KO photoreceptors, suggesting that apoptosis was prevalent. Taken together, our findings indicate that mGPx4 is essential for the maturation of cone photoreceptors but not for the maturation of rod photoreceptors, although it is still critical for the survival of rod photoreceptors after maturation. In conclusion, we reveal novel functions of mGPx4 in supporting development and survival of photoreceptors in vivo.

Macular and peripapillary retinal nerve fiber layer thinning in eyes with prediabetes in the elderly population: OTASSHA study.

PURPOSE: To investigate retinal thickness parameters in the elderly with prediabetes mellitus (preDM) and type 2 DM without retinopathy (non-diabetic retinopathy [NDR]). METHODS: This cross-sectional study included a total of 1273 eyes without retinal pathologies of 699 volunteers aged ≥ 65 years were included. The eyes were categorized into non-DM (606 eyes), preDM (480 eyes), and NDR (187 eyes) groups according to their HbA1c levels. Fundus photography, swept-source optical coherence tomography, and comprehensive systemic examination were conducted. The thicknesses of the retinal nerve fiber layer in the macula (mRNFL) and peripapillary (pRNFL), ganglion cell complex (GCC), and ganglion cell inner plexiform layer (GCIPL), as well as central subfield thickness (CST) and central foveal thickness (CFT) were investigated for their association with DM stage using linear mixed model. RESULTS: A statistically significant thinning of mRNFL was observed in preDM vs. non-DM and in NDR vs. preDM in 3/6 sectors. A significant thinning of pRNFL was observed in preDM vs. non-DM and in NDR vs. preDM in 2/12 sectors. Such DM stage-dependent thinning of RNFL was observed mainly in the temporal and superior sectors. GCIPL and GCC were less sensitive to reflect DM-dependent inner retinal thinning. CST and CFT were not significantly associated with different DM stages. CONCLUSION: The thinning of mRNFL in the temporal and superior sectors might be a sensitive parameter associated with early neurodegeneration in preDM and NDR.

ASSOCIATION OF PREDIABETES WITH RETINAL MICROVASCULATURE ON SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN THE ELDERLY: OTASSHA Study.

PURPOSE: To investigate the retinal microvasculature in the elderly persons with prediabetes mellitus (preDM) and type 2 DM. METHODS: This cross-sectional study included a total of 452 eyes without retinal pathologies of 301 elderly volunteers aged ≥65 years, and they were categorized into nonDM (225 eyes), preDM (177 eyes), and DM (50 eyes) groups based on their HbA1c. Fundus photography, swept-source optical coherence tomography and angiography, and comprehensive systemic examinations were conducted. Vessel density (VD) and foveal avascular zone in superficial and deep retinal microvasculature were investigated for their association with DM stages using linear mixed model. RESULTS: Superficial VD (sVD) mean values in nonDM, preDM, and DM groups were 35.2%, 34.9%, and 34.8%, respectively. sVD in preDM was equivalent to sVD in DM, whereas significantly lower compared with sVD in nonDM (difference [95% CI] -0.19 [-0.33 to -0.049], P = 0.009). Deep VD (dVD) mean values in nonDM, preDM, and DM groups were 35.0%, 35.0%, and 34.4%, respectively. dVD in preDM was equivalent to dVD in nonDM, whereas significantly higher compared with dVD in DM (difference [95% CI] 0.31 [0.046-0.57], P = 0.02). There was no significant association between foveal avascular zone area and DM stages. CONCLUSION: Retinal microvasculature may be affected at the prediabetic stage in the elderly.

Influence of surface light scattering in hydrophobic acrylic intraocular lenses on laser beam transmittance.

The aim of this study was to experimentally examine the changes in the transmittances of photocoagulation lasers when surface light scattering increases in AcrySof intraocular lenses (IOLs). SA60AT IOLs (Alcon) were acceleratingly aging for 0, 3, 5, and 10 years to simulate surface light scattering, and the surface light-scattering intensities of both IOL surfaces were measured using a Scheimpflug photographer. The powers of laser beams that passed from a laser photocoagulator through the aged IOLs were measured at 532, 577, and 647 nm. Changes in the laser power and transmittance with the years of aging and the intensities of surface light scattering were examined. Although the intensity of surface light scattering increased with the years of aging, the laser power did not change with the years of aging (P > 0.30, Kruskal-Wallis test). There were no significant changes in the laser transmittance with the years of aging or the laser wavelength (P > 0.30 and 0.57, respectively). The intensity of surface light scattering revealed no significant association with the laser transmittance at any wavelength (P > 0.37, liner regression). The increases in the surface light scattering of the AcrySof IOLs would not influence retinal photocoagulation treatments for up to 10 years after implantation.

Optimal area of retinal photocoagulation necessary for suppressing active iris neovascularisation associated with diabetic retinopathy.

To determine the optimal area of retinal photocoagulation required for suppressing active neovascularisation (NVI) associated with diabetic retinopathy. We studied 1 eye each of 4 patients in whom active NVI was ophthalmoscopically shown to have been suppressed by additional photocoagulation. These patients initially underwent pan-retinal photocoagulation for diabetic retinopathy at another hospital, but NVI developed subsequently. We compared the areas of photocoagulation before and after additional photocoagulation and compared the area of retinal photocoagulation. The photocoagulated areas before and after additional photocoagulation in the four eyes were 20.7 and 45.2, 36.6 and 56.3, 30.4 and 67.4, and 11.7 and 53.4 %, respectively. The area of retinal photocoagulation required to suppress active NVI is calculated to be ~50 %.

The role of lipid peroxidation in epithelial-mesenchymal transition of retinal pigment epithelial cells.

Epithelial-Mesenchymal Transition (EMT) of retinal pigment epithelial (RPE) cells is recognized as pivotal in various retinal diseases. Previous studies have suggested a reciprocal regulation between reactive oxygen species (ROS) and EMT, though the involvement of peroxidized lipids or the effects of reducing them has remained unclear. The present study disclosed that EMT of ARPE-19 cells induced by TGF-ß2 and TNF-α involves increased lipid peroxidation, and Ferrostatin-1 (Fer-1), a lipophilic antioxidative agent, successfully inhibited the increase in lipid peroxidation. Fer-1 suppressed the formation of EMT-associated fibrotic deposits, while EMT induction or Fer-1 treatment did not influence the cell viability or proliferation. Functionally, Fer-1 impeded EMT-driven cell migration and reduction in transepithelial electrical resistance. It demonstrated regulatory prowess by downregulating the mesenchymal marker fibronectin, upregulating the epithelial marker ZO-1, and inhibiting the EMT-associated transcriptional factor ZEB1. Additionally, VEGF, a major pathogenic cytokine in various retinal diseases, is also upregulated during EMT, and Fer-1 significantly mitigated the effect. The present study disclosed the involvement of lipid peroxidation in EMT of RPE cells, and suggests the suppression of lipid peroxidation may be a potential therapeutic target in retinal diseases in which EMT is implicated.

Postoperative vision loss due to bilateral vitreous hemorrhage after robot-assisted laparoscopic hysterectomy: A case report.

Purpose: To report a case of bilateral vitreous hemorrhage (VH) resulting in postoperative vision loss (POVL) after robot-assisted laparoscopic hysterectomy in a 71-year-old female patient. Observations: At initial presentation, best-corrected visual acuity was hand motion at 20 cm in the right eye and 20/666 in the left eye. VH in both eyes and preretinal hemorrhage in the left eye was observed. As the hemorrhage gradually resolved, a full-thickness macular hole was discovered in the right eye, for which the patient did not agree with a surgical treatment. Conclusions and importance: This report describes a rare incidence of bilateral VH as a cause of POVL after non-ophthalmic surgery, which may be related to Trendelenburg positioning, CO2 pneumoperitoneum, and a long surgical duration. Given that POVL can cause severe visual impairment, consultation with ophthalmologists is crucial.

Encircling continuous suture technique for the management of extensive traumatic cyclodialysis: A case report.

PURPOSE: To report a surgical technique of cyclopexy, wherein two laps of encircling continuous sutures are placed around the limbus to treat refractory extensive cyclodialysis. METHODS: Color fundus photography, swept-source optical coherence tomography (OCT) for the anterior segment, and spectral-domain OCT for the macula. RESULTS: Previous attempts, including indirect cyclopexy and direct external cyclopexy with gas injection, failed to successfully resolve the severe cyclodialysis and associated hypotonic maculopathy. In the third surgery, two laps of encircling continuous sutures were placed around the limbus at the distances of 2-3 mm and 3-4 mm, along with phacoemulsification, intraocular lens implantation, and capsular tension ring placement. Following the surgery, hypotony and hypotonic maculopathy were effectively resolved, resulting in a significant improvement in visual acuity, that has been maintained over a year. CONCLUSION: The described surgical technique of encircling continuous sutures may be a viable option for the treatment of severe cyclodialysis.

Navigated direct photocoagulation with a 30-ms short-pulse laser for treating microaneurysms in diabetic macular edema exhibits a high closure rate.

This study carried out direct photocoagulation for treating microaneurysms (MAs) in diabetic macular edema (DME) using a navigation laser system with a 30-ms pulse duration. The MA closure rate after 3 months was investigated using pre and postoperative fluorescein angiography images. MAs primarily inside the edematous area based on optical coherence tomography (OCT) maps were selected for treatment, and leaking MAs (n = 1151) were analyzed in 11 eyes (eight patients). The total MA closure rate was 90.1% (1034/1151), and the mean MA closure rate in each eye was 86.5 ± 8.4%. Mean central retinal thickness (CRT) decreased from 471.9 ± 73.0 µm to 420.0 ± 87.5 µm (P = 0.049), and there was a correlation between the MA closure rate and the CRT reduction rate (r = 0.63, P = 0.037). There was no difference in the MA closure rate depending on the degree of edema thickness based on a false-color topographic OCT map image. Direct photocoagulation for DME with a short pulse using the navigated photocoagulator resulted in a high MA closure rate in just 3 months and a corresponding improvement in retinal thickness. These findings encourage the use of a new therapeutic approach for DME.

Microperimetric analysis of diabetic macular edema after navigated direct photocoagulation with short-pulse laser for microaneurysms.

BACKGROUND: Focal laser photocoagulation is an important treatment option for diabetic macular edema (DME). This study aimed to examine the retinal sensitivity (RS) and morphological changes at the coagulated site after direct photocoagulation of microaneurysms (MAs) in patients with DME using a navigated laser photocoagulator with a short-pulse duration of 30 ms. METHODS: Images of early-phase fluorescein angiography were merged with images from the optical coherence tomography (OCT) map with 9 Early Treatment Diabetic Retinopathy Study grid circles, and MAs inside the edema area were selected for direct photocoagulation. The best-corrected visual acuity (BCVA), parameters of the OCT map including central retinal thickness and retinal thickness in edema range, central RS, and RS in the edema area were assessed at 1 and 3 months after the laser treatment. The RS points that overlapped with the laser spots were identified by merging the Navilas' digital treatment reports and the microperimetry images. RESULTS: Seventeen eyes from 14 patients were studied. The mean retinal thickness in the edema range decreased at 3 months compared with pretreatment (P = 0.042), but the BCVA, central retinal thickness, central RS, and RS in the edema area remained unchanged. Overall, 32 of 400 sensitivity points overlapped with the laser-coagulated spots. The mean RS at these spots were 22.4 ± 5.3 dB at 1 month and 22.5 ± 4.8 dB at 3 months, with no significant change from the baseline of 22.7 ± 3.5 dB. CONCLUSIONS: Retinal thickness improved in the coagulated edema area without a decrease in RS after direct photocoagulation of MAs with a short 30-ms pulse using Navilas. This promising therapeutic strategy for DME is effective and minimally invasive.

Optical coherence tomography findings after surgery for sub-inner limiting membrane hemorrhage due to ruptured retinal arterial macroaneurysm.

Ruptured retinal arterial macroaneurysm (RAM) can cause sub-inner limiting membrane (ILM) hemorrhage, leading to acute vision loss in the elderly. Vitrectomy has been established as an effective treatment to remove hemorrhage and facilitate visual recovery. Although optical coherence tomography (OCT) is useful for the diagnosis of sub-ILM hemorrhage before surgery, little is known about the postoperative OCT findings. Here, we retrospectively investigated the records of nine eyes of nine patients who underwent surgery for sub-ILM hemorrhage due to RAM rupture. On postoperative OCT, hyperreflectivity throughout the full thickness of the central fovea was observed in eight eyes (88.9%), and disruption of the ellipsoid/interdigitation zone (EZ/IZ) was observed in seven out of eight eyes (87.5%). The widths of the hyperreflectivity and EZ disruption gradually decreased. Visual recovery was least favorable in two eyes, in which the EZ line continuation did not recover until the final follow-up. The OCT findings corresponded to the hemorrhagic staining identified on fundus photographs in at least four eyes; as per the fundus photographs the findings persisted even after the hemorrhage was absorbed. In contrast, the OCT findings resembled the appearance before the development of a full-thickness macular hole, suggesting fragility caused by the RAM rupture.

Differential gene expression analysis using RNA sequencing: retinal pigment epithelial cells after exposure to continuous-wave and subthreshold micropulse laser.

PURPOSE: Subthreshold micropulse laser (SMPL) is more clinically efficient for the treatment of diabetic macular edema (DME) than the conventional continuous-wave (CW) laser. We aimed to characterize transcriptome changes after the application of these lasers and to compare the transcripts. METHODS: Human pluripotent stem cell-derived retinal pigment epithelial cells were exposed to laser irradiation. Differentially expressed genes (DEGs), distribution of heat shock protein (Hsp) family, gene expression profile, and gene ontology (GO) enrichment analysis based on RNA sequencing data were investigated at 3 h and 24 h after irradiation. RESULTS: CW laser induced more DEGs than SMPL (1771 vs. 520 genes). The expression of the Hsp family was confirmed in both groups: however, the induction patterns was different for different genes. GO enrichment analysis revealed that CW laser upregulated the expression of DEGs involved in vasculature development (GO: 0001944), related to apoptosis and repair after cell injury whereas SMPL upregulated the expression of DEGs involved in photoreceptor cell maintenance (GO: 0045494), photoreceptor cell development (GO: 0042461), and sensory perception of light stimuli (GO: 0050953). CONCLUSIONS: The results provide insights into the genetic responses and may contribute to the understanding of the molecular mechanisms of laser-induced thermal effects.

A force measurement platform for a vitreoretinal surgical simulator using an artificial eye module integrated with a quartz crystal resonator.

To provide quantitative feedback on surgical progress to ophthalmologists practicing inner limiting membrane (ILM) peeling, we developed an artificial eye module comprising a quartz crystal resonator (QCR) force sensor and a strain body that serves as a uniform force transmitter beneath a retinal model. Although a sufficiently large initial force must be loaded onto the QCR force sensor assembly to achieve stable contact with the strain body, the highly sensitive and wide dynamic-range property of this sensor enables the eye module to detect the slight forceps contact force. A parallel-plate strain body is used to achieve a uniform force sensitivity over the 4-mm-diameter ILM peeling region. Combining these two components allowed for a measurable force range of 0.22 mN to 29.6 N with a sensitivity error within -11.3 to 4.2% over the ILM peeling area. Using this eye module, we measured the applied force during a simulation involving artificial ILM peeling by an untrained individual and compensated for the long-term drift of the obtained force data using a newly developed algorithm. The compensated force data clearly captured the characteristics of several types of motion sequences observed from video recordings of the eye bottom using an ophthalmological microscope. As a result, we succeeded in extracting feature values that can be potentially related to trainee skill level, such as the mean and standard deviation of the pushing and peeling forces, corresponding, in the case of an untrained operator, to 122.6 ± 95.2 and 20.4 ± 13.2 mN, respectively.

Bionic eye system mimicking microfluidic structure and intraocular pressure for glaucoma surgery training.

Among increasing eye diseases, glaucoma may hurt the optic nerves and lead to vision loss, the treatment of which is to reduce intraocular pressure (IOP). In this research, we introduce a new concept of the surgery simulator for Minimally Invasive Glaucoma Surgery (MIGS). The concept is comprised of an anterior eye model and a fluidic circulatory system. The model made of flexible material includes a channel like the Schlemm's canal (SC) and a membrane like the trabecular meshwork (TM) covering the SC. The system can monitor IOP in the model by a pressure sensor. In one of the MIGS procedures, the TM is cleaved to reduce the IOP. Using the simulator, ophthalmologists can practice the procedure and measure the IOP. First, considering the characteristics of human eyes, we defined requirements and target performances for the simulator. Next, we designed and manufactured the prototype. Using the prototype, we measured the IOP change before and after cleaving the TM. Finally, we demonstrated the availability by comparing experimental results and target performances. This simulator is also expected to be used for evaluations and developments of new MIGS instruments and ophthalmic surgery robots in addition to the surgical training of ophthalmologists.

Surgical Treatment for a Full-Thickness Macular Hole That Developed on a Large Drusenoid Pigment Epithelial Detachment.

Full-thickness macular hole (FTMH) and age-related macular degeneration (AMD) can affect the same eyes in the older population. Previously reported phenotypes of AMD concurrent with FTMH include early/intermediate AMD and serous pigment epithelial detachment (PED). A 68-year-old woman presented to our clinic with decreased vision due to a cataract and a large drusenoid PED in both eyes. After ruling out choroidal neovascularization, she underwent cataract surgery. Three days after the cataract surgery, an FTMH was found in the left eye. Although the FTMH was not closed after the initial pars plana vitrectomy (PPV) with the inner limiting membrane (ILM) peeling and air tamponade, it was closed after reoperation with additional ILM peeling, retinal massage, and SF6 gas tamponade. Best-corrected visual acuity (BCVA) was improved from 20/60 before the first PPV to 20/40 at six months after the reoperation. Some large soft drusen in the macula were fused after surgeries in the operated eye, but not in the fellow eye. An FTMH concurrent with a large drusenoid PED is rare. It can be closed surgically, and postoperative visual function can improve.

Fovea-Sparing as Opposed to Total Peeling of Internal Limiting Membrane for Myopic Foveoschisis: A Systematic Review and Meta-analysis.

TOPIC: The effectiveness of fovea-sparing (FS) peeling of internal limiting membrane (ILM) to treat myopic foveoschisis (MF) has not been understood fully. The present meta-analysis aimed to compare postoperative visual and anatomic outcomes between FS peeling and total peeling (TP) of ILM in pars plana vitrectomy for the treatment of MF. CLINICAL RELEVANCE: Postoperative macular hole (MH) development is not uncommon and is a serious complication after surgery for MF, with poor visual prognosis. Fovea-sparing peeling of ILM is expected to reduce the risk of postoperative MH; however, no statistically significant evidence exists to prove this hypothesis. In addition, its effect on postoperative visual acuity has not been clear. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were reviewed systematically, and studies that compared FS with total ILM peeling in MF surgery were retrieved. The protocol was registered in International Prospective Register of Systematic Reviews (identifier, CRD42020201675). Primary outcome measures were the postoperative best-corrected visual acuity (BCVA) and frequency of postoperative MH development. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Eight studies with 300 eyes from 289 patients were included. All studies were nonrandomized and observational. The postoperative BCVA was significantly better in eyes treated with FS (mean difference [MD], -0.15 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.24 to -0.05 logMAR; P = 0.002). The risk of postoperative MH was significantly lower in the FS group (odds ratio, 0.19; 95% CI, 0.06-0.56; P = 0.003). No significant difference was found in postoperative central foveal thickness (MD, 12.59 µm; 95% CI, -2.8 to 28.0 µm; P = 0.11). The certainty of evidence regarding lower frequency of postoperative MH after FS peeling was considered moderate, whereas the certainty regarding better postoperative BCVA after FS peeling was judged to be low. DISCUSSION: Fovea-sparing peeling may contribute to better visual acuity outcome and lower risk of postoperative MH development in eyes with MF.

Changes in entropy on polarized-sensitive optical coherence tomography images after therapeutic subthreshold micropulse laser for diabetic macular edema: A pilot study.

PURPOSE: To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. RESULTS: A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). CONCLUSION: Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. CLINICAL TRIAL: This clinical study was registered in UMIN-CTR (ID: UMIN000042420).

Correlation between anterior chamber flare changes and diabetic macular edema after intravitreal injection of ranibizumab and aflibercept.

PURPOSE: To evaluate aqueous flare change patterns following anti-vascular endothelial growth factor therapy for diabetic macular edema (DME) and investigate the relationship between changes in flare values and central macular thickness (CMT). STUDY DESIGN: Retrospective, interventional case series METHODS: A total of 84 eyes of 62 patients with DME received either intravitreal ranibizumab (IVR; n = 62) or aflibercept (IVA; n = 22). A laser flare photometer (Kowa FM500, Kowa Company, Ltd) was used to measure flare values, and CMT was assessed using optical coherence tomography. Flare values and CMT were measured prior to injection (baseline) and at, 1, 7 and 14 days after injection. RESULTS: Flare values in the IVR group decreased significantly at day 14 (P = 0.001), whereas the IVA group showed a significant increase in flare values at day 1 (P < 0.001). In the IVA group, the baseline flare values were significantly higher in the CMT reduction group than in the non-CMT reduction group (P = 0.035). There was no correlation between changes in flare values and CMT either in the IVA or IVR group. CONCLUSIONS: Flare value changes in patients treated with IVR decreased at day 14 post-injection. This may indicate when the most anti-inflammatory effect was obtained. There was no correlation between changes in flare values and CMT either in the IVA or IVR group; nevertheless, our research suggests that the baseline flare value is a predictive factor for the efficacy of IVA in DME.

Ursodeoxycholic Acid Attenuates the Retinal Vascular Abnormalities in Anti-PDGFR-ß Antibody-Induced Pericyte Depletion Mouse Models.

As a clinical manifestations of diabetic retinopathy (DR), pericytes (PCs) loss from the capillary walls is thought to be an initial pathological change responsible for the breakdown of the blood-retinal barrier (BRB). This study was performed to investigate the effects of ursodeoxycholic acid (UDCA) in PC depletion mice by injection of an antibody against platelet-derived growth factor reception-ß (PDGFR-ß clone APB5). To assess the integrity of the retinal vessels, their density, diameters, vessel branching points, and number of acellular capillaries were evaluated. While all types of retinal vessels became enlarged in APB5-induced mice, treatment with UDCA rescued the vasculature; the vessel density, diameter of the veins and capillaries, and vessel branching points were significantly lower in mice treated with UDCA. Although APB5-induced mice displayed progressive exacerbation of retinal edema, whole retinal thickness upon treatment with UDCA was significantly decreased. Additionally, UDCA reduced the expression of F4/80+ macrophages in the APB5-induced retina according to immunofluorescent labeling. UDCA also reduced the increased expression of angiogenic factors and inflammatory mediators (vascular endothelial growth factor, intercellular adhesion molecule-1, and monocyte chemotactic protein-1). These findings suggest that UDCA can be used to prevent the progression of and treat DR.