Impairment of flicker-induced increase in retinal blood flow in diabetic pigs.

PURPOSE: To evaluate retinal blood flow (RBF) regulation in response to RBF stress in maturity-onset diabetes of the young type 3 (MODY3) pigs. STUDY DESIGN: Case-control study. METHODS: MODY3 pigs (diabetes mellitus [DM] group, n = 8) transfected with the human mutant hepatocyte nuclear factor-1⍺ and normal pigs of the same age (normal group, n = 8) were used as subjects. After confirming DM onset, the experiment was performed under inhalation anesthesia with isoflurane at 2 months of age before the cataract progressed. Ocular blood flow was assessed by calculating the optic papillary mean blur rate using laser speckle flowgraphy, modified for pig eye measurements. After baseline ocular blood flow measurements, flicker stimulation (12 Hz, 3 min) was applied, and ocular blood flow was measured over time. RESULTS: Blood glucose was 81.8 ± 5.1 mg/dL in the normal group and 311.4 ± 23.1 mg/dL in the DM group (mean ± standard error). The percent change in ocular blood flow at 3 min after flicker stimulation was +31.0 ± 10.9% in the normal group and -6.6 ± 6.5% in the DM group compared to the preload value, and the difference was statistically significant (Mann-Whitney test, P = 0.015). CONCLUSION: RBF response to flicker stimulation is reduced at 2 months of age in MODY3 pigs, suggesting that retinal neurovascular coupling is impaired from the early onset of DM.

Effects of switching from intravitreal injection of aflibercept to faricimab on ocular blood flow in patients with diabetic macular edema.

We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with treatment-resistant diabetic macular edema (DME). The medical records of 15 patients with DME who had received IVA injection ≥ 3 months before were retrospectively reviewed. The best-corrected visual acuity, central macular thickness (CMT) on optical coherence tomography, and mean blur rate (MBR) of all disc areas on laser speckle flowgraphy were measured before, 1 week after, and 4 weeks after IVA and IVF, respectively. The changes in visual acuity showed no significant difference after switching from IVA to IVF (P = 0.732). The mean CMT decreased significantly during the follow-up period (both P < 0.001). MBR showed no significant difference during the follow-up period (P = 0.26). However, it decreased significantly 4 weeks after IVF (P = 0.01) compared with the baseline value, but not 4 weeks after IVA (P = 0.074). A significant association was observed between decreased MBR and decreased CMT in patients who received IVF (correlation coefficient: 0.501, P = 0.005) but not in those who received IVA (P = 0.735). Thus, IVF maintained ocular blood flow reduction, although no significant differences in visual acuity and CMT changes were observed compared to IVA.

Successful prism treatment for cyclic esotropia: A case report.

Purpose: To report a case of cyclic esotropia successfully treated with prismatic correction. Observations: A 9-year-old girl presented with intermittent esotropia and diplopia occurring over the previous 4 months. The patient had 30 prism diopters (PD) of esotropia at both distance and near. Ocular motility testing, other ophthalmic examinations, and brain magnetic resonance imaging revealed no abnormalities. At the third visit, the patient had 6 PD of intermittent esotropia without diplopia, and the eye position diary demonstrated esotropia every other day, which led to a diagnosis of cyclic esotropia with a 48-h cycle. The cyclic pattern persisted for 9 months following the initial visit. However, during a subsequent regular visit, the patient reported a newfound ability to self-adjust from "esotropic" days to "straight" days by tightly closing the eyes immediately after waking up in the morning, particularly when wishing to avoid strabismus. To address the condition, we affixed a Fresnel membrane prism on the glasses to compensate for the latent deviation on a "straight" day. During the subsequent 18 months, the esotropia completely resolved, and the patient was followed up with gradual decreases in prism power. Conclusions and Importance: Correcting latent deviation using a prism lens is a simple approach without potential side effects. The present findings suggest that this approach is a viable treatment option for cyclic esotropia during its early and periodic stages.

The Effect of Anti-Autotaxin Aptamers on the Development of Proliferative Vitreoretinopathy.

This study investigated the effect of anti-autotaxin (ATX) aptamers on the development of proliferative vitreoretinopathy (PVR) in both in vivo and in vitro PVR swine models. For the in vitro study, primary retinal pigment epithelial (RPE) cells were obtained from porcine eyes and cultured for cell proliferation and migration assays. For the in vivo study, a swine PVR model was established by inducing retinal detachment and injecting cultured RPE cells (2.0 × 106). Concurrently, 1 week after RPE cell injection, the anti-ATX aptamer, RBM-006 (10 mg/mL, 0.1 mL), was injected twice into the vitreous cavity. Post-injection effects of the anti-ATX aptamer on PVR development in the in vivo swine PVR model were investigated. For the in vitro evaluation, the cultured RPE cell proliferation and migration were significantly reduced at anti-ATX aptamer concentrations of 0.5-0.05 mg and at only 0.5 mg, respectively. Intravitreal administration of the anti-ATX aptamer also prevented tractional retinal detachment caused by PVR in the in vivo PVR model. We observed that the anti-ATX aptamer, RBM-006, inhibited PVR-related RPE cell proliferation and migration in vitro and inhibited the progression of PVR in the in vivo model, suggesting that the anti-ATX aptamer may be effective in preventing PVR.

A case of acute syphilitic posterior placoid chorioretinitis showing improved choroidal blood flow after treatment.

Purpose: Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare form of ocular syphilis. However, its pathophysiology is not fully understood. Laser speckle flowgraphy (LSFG) can facilitate the non-invasive evaluation of blood flow and allow investigations into the effects of treatments in various ocular diseases. We report a case of ASPPC that presented with symptoms only in the right eye but showed bilateral disease in LSFG. Observations: A 54-year-old man presented with decreased vision and visual field defects in the right eye 2 days prior to the initial visit. Fundoscopy images showed a typical yellowish placoid lesion in the macular area, and optical coherence tomography showed disruption of the outer retinal layers and nodular appearance of the retinal pigment epithelium. Fluorescence angiography showed excessive leakage of the placoid lesion characterized by hypofluorescent dots in the inner area ("leopard spotting"). The patient was diagnosed with unilateral ASPPC based on multiple imaging and serological tests. Penicillin was administered for 2 weeks, and the patient showed improvement in symptoms and restoration of the retinal structure. The mean blur rate of the right/left eye was 2.1/5.9 arbitrary units (AU) before treatment and increased to 4.5/9.3 AU 6 months after treatment. Conclusions and importance: Despite the absence of typical imaging signs and symptoms in the left eye, both eyes may have been affected with different degrees of severity. Thus, LSFG may facilitate the evaluation of treatment effects and the prediction of ocular inflammatory diseases in the early stages.

A Case of Bilateral Frosted Branch Angiitis after mRNA COVID-19 Vaccination.

We report a case of bilateral frosted branch angiitis (FBA) following mRNA-1273 COVID-19 vaccination. A 79-year-old male was referred to our hospital with a sudden onset of blurred vision in the right eye, which occurred during his return home after receiving the third dose of a messenger RNA (mRNA) COVID-19 vaccine. Fundoscopy revealed severe retinal vasculitis with sheathing of the artery and vein in the right eye more so than in the left eye, suggestive of bilateral FBA. Optical coherence tomography showed significant macular edema and serous retinal detachment in the right eye. Polymerase chain reaction assay detected Epstein-Barr virus (EBV) in the aqueous humor, and antibody against the EBV viral capsid antigen was positive for IgM. The next day, best-corrected visual acuity (BCVA) worsened to 0.08 due to macular edema in the left eye. After 2 courses of pulse steroid therapy and intravenous infusion of acyclovir, macular edema had disappeared and sheathing of retinal vessels was improving. At 5 months after the mRNA COVID-19 vaccination, BCVA was maintained 0.15 in the right eye and 0.7 in the left eye. Severe uveitis, such as FBA, can occur after mRNA COVID-19 vaccination.

Dilation of porcine retinal arterioles to nobiletin, a polymethoxyflavonoid: Roles of nitric oxide and voltage-dependent potassium channel.

We examined the effects of nobiletin, a polymethoxyflavonoid, on the retinal microvascular diameter to determine if they depend on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to nobiletin. The retinal arterioles dilated in a nobiletin concentration-dependent (100 pM-10 µM) manner and decreased by 50% after endothelial removal. The nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), reduced nobiletin-induced vasodilation comparable to denudation. Blockade of soluble guanylyl cyclase by 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) produced a similar inhibitory effect as that by L-NAME. Nobiletin-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium (TEA), and the voltage-gated K (Kv) inhibitor, 4-aminopyridine. Co-administration of L-NAME and TEA almost eliminated nobiletin-induced vasodilation. Nobiletin elicits both endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and Kv channel activation, respectively.

A pilot study of diabetic retinopathy in a porcine model of maturity onset diabetes of the young type 3 (MODY3).

Diabetic retinopathy (DR) is a leading cause of blindness in the working population. Because novel therapeutic intervention require testing, there is an urgent need for reliable animal models that faithfully replicate DR. Pig eyes have many similarities to human eyes anatomically and physiologically. Thus, attempts have been made to establish porcine models of DR by surgical, pharmaceutical or genetical induction of insulin deficiency, and dietary intervention. A previous study reported a transgenic pig model of maturity onset diabetes of the young type 3 (MODY3) developed signs of severe DR such as hemorrhage and proliferative tissue at the surface of the retina. However, the course of development of DR has not been studied in detail in this model. The purpose of this study was to investigate the early phase of DR in a MODY3. MODY3 and wild-type (WT) pigs underwent fundus photography and fluorescein angiogram (FA) before they developed cataracts. Animals were euthanized at age 1, 4, 7, and 10 months. Whole-mount retina and 10-µm thick paraffinized sections were stained with isolectin B4, and vessel density was determined by MATLAB software. At 4 and 7 months, retinal arterioles were immediately cannulated, and vasomotor action was measured by incubation with bradykinin and sodium nitroprusside. In the MODY3 pigs, fasting blood sugar levels gradually increased up to 500 mg/dL. Vascular tortuosity and yellowish spindle-shaped lesions were confirmed in MODY3 pigs at the age of 7 months; however, no microaneurysms were detected on FA. Compared with age-matched WT pigs, MODY3 pigs showed a significant decrease in blood vessel density in the intermediate and deep vascular plexus at 4 and 7 months of age and a slight decrease in capillary density in the superficial vascular plexus at 7 months of age. In MODY3 pigs, electron microscopy revealed thickening of the capillary basement membrane and leukostasis in the major blood vessels at 10 months of age. Bradykinin-induced dilation of retinal arterioles was diminished in MODY3 pigs as early as 7 months of age. Within 1 year after birth, MODY3 pigs show all typical early vascular lesions of diabetes except for microaneurysm formation. This pilot study suggests that the MODY3 pigs may serve as a suitable DR model to test effects of newly developed compounds on DR.

Comparison of Postoperative Stability of Intraocular Lenses after Phacovitrectomy for Rhegmatogenous Retinal Detachment.

We retrospectively compared the stability of intraocular lenses (IOLs) routinely used at our institution by measuring IOL position after phacovitrectomy for rhegmatogenous retinal detachment (RRD). Patients with RRD who underwent phacovitrectomy with gas tamponade received one of three IOLs: 6-mm, single-piece NS-60YG (NIDEK, 15 eyes); 6-mm, single-piece XY1 (HOYA, 11 eyes); or 7-mm, three-piece X-70 (Santen, 11 eyes). Various parameters associated with the anterior chamber, lens, and IOL were measured by swept-source anterior segment optical coherence tomography (CASIA2; Tomey Corp) before and 1 week and 1 month after surgery. IOL position was determined as follows: IOL position = (postoperative aqueous depth [AQD] − preoperative AQD)/lens thickness. We found no significant difference in axial length between the IOLs (p = 0.97). At 1 week, IOL position was as follows: NS-60YG, 0.32; XY1, 0.24; and X-70, 0.26 (p < 0.05). The respective IOL positions at 1 month were 0.35, 0.27, and 0.28 (p < 0.01). These results indicated the smallest anterior shift with NS-60YG. To replicate the anterior shift of IOL position ex vivo, biomechanical measurement was performed. NS-60YG resisted more displacement force than the other IOLs. Thus, in eyes undergoing phacovitrectomy for RRD, NS-60YG was the most stable of the three IOLs studied.

Beneficial Effect of Long-Term Administration of Supplement With Trapa Bispinosa Roxb. and Lutein on Retinal Neurovascular Coupling in Type 2 Diabetic Mice.

Purpose: We investigated the effect of long-term administration of supplement with trapa bispinosa roxb. extract (TBE) and lutein on the susceptibility of retinal blood flow regulation in type 2 diabetic mice. Methods: Six-week-old db/db mice were randomly divided into the untreated group (n = 6) and the treated group received the supplement with TBE and lutein (n = 6). The longitudinal changes in retinal blood flow responses to systemic hyperoxia and a flicker stimulation were evaluated every 2 weeks in diabetes db/db mice from age 8 to 14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of glial fibrillary acid protein (GFAP) and vascular endothelial growth factor (VEGF) by immunofluorescence. Results: The resting retinal blood flow was steady and comparable between two groups throughout the study. In db/db mice with supplement, both blood flow responses were restored from 8 to 14 weeks of age compared with diabetic mice treated with the placebo. Supplement prevented the activation of GFAP and decreased the expression of VEGF detected by immunofluorescence compared with the diabetic mice treated with placebo. Conclusion: We found that the long-term administration of supplement with TBE and lutein improved the impaired regulation of retinal blood flow in response to systemic hyperoxia and flicker stimulation, suggesting that these supplements can prevent diabetic retinopathy by improving abnormal neurovascular coupling in type 2 diabetic mice.

Fenofibrate Nano-Eyedrops Ameliorate Retinal Blood Flow Dysregulation and Neurovascular Coupling in Type 2 Diabetic Mice.

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8-14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice.

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice.

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.

Comprehensive assessment of systemic arteriosclerosis in relation to the ocular resistive index in acute coronary syndrome patients.

This study aimed to investigate the relationship between ocular vascular resistance parameters, evaluated by laser speckle flowgraphy (LSFG), and systemic atherosclerosis, renal parameters and cardiac function in acute coronary syndrome (ACS) patients. We evaluated 53 ACS patients between April 2019 and September 2020. LSFG measured the mean blur rate (MBR) and ocular blowout time (BOT) and resistivity index (RI). 110 consequent patients without a history of coronary artery disease who visited ophthalmology as a control group. Significant positive correlations were observed between ocular RI and systemic parameters in ACS patients, including intima-media thickness (r = 0.34, P = 0.015), brachial-ankle pulse-wave velocity (r = 0.41, P = 0.002), cystatin C (r = 0.32, P = 0.020), and E/e' (r = 0.34, P = 0.013). Ocular RI was significantly higher in the ACS group than in the control group in male in their 40 s (0.37 ± 0.02 vs. 0.29 ± 0.01, P < 0.001) and 50 s (0.36 ± 0.02 vs. 0.30 ± 0.01, P = 0.01). We found that the ocular RI was associated with systemic atherosclerosis, early renal dysfunction, and diastolic cardiac dysfunction in ACS patients, suggesting that it could be a useful non-invasive comprehensive arteriosclerotic marker.

Effect of prorenin peptide vaccine on the early phase of diabetic retinopathy in a murine model of type 2 diabetes.

Prorenin is viewed as an ideal target molecule in the prevention of diabetic retinopathy. However, no drugs are available for inhibiting activation of prorenin. Here, we tested the effect of a prorenin peptide vaccine (VP) in the retina of a murine model of type 2 diabetes (T2D). To choose the optimal vaccine, we selected three different epitopes of the prorenin prosegment (E1, E2, and E3) and conjugated them to keyhole limpet hemocyanin (KLH). We injected C57BL/6J mice twice with KLH only (as a control vaccine), E1 conjugated with KLH (E1-KLH), E2-KLH, or E3-KLH and compared antibody titers. E2-KLH showed the highest antibody titer and specific immunoreactivity of anti-sera against prorenin, so we used E2-KLH as VP. Then, we administered injections to the non-diabetic db/m and diabetic db/db mice, as follows: db/m + KLH, db/db + KLH, and db/db + VP. Retinal blood flow measurement with laser speckle flowgraphy showed that the impaired retinal circulation response to both flicker light and systemic hyperoxia in db/db mice improved with VP. Furthermore, the prolonged implicit time of b-wave and oscillatory potentials in electroretinography was prevented, and immunohistochemical analysis showed reduced microglial activation, gliosis, and vascular leakage. The enzyme-linked immunosorbent spot assay confirmed vaccinated mice had no auto-immune response against prorenin itself. The present data suggest that vaccination against prorenin is an effective and safe measure against the early pathological changes of diabetic retinopathy in T2D.

The Impact of Interval between Recurrence and Reinjection in Anti-VEGF Therapy for Diabetic Macular Edema in Pro Re Nata Regimen.

BACKGROUND: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. METHODS: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. RESULTS: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). CONCLUSION: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

Retinal blood flow dysregulation precedes neural retinal dysfunction in type 2 diabetic mice.

We investigated and compared the susceptibility of retinal blood flow regulation and neural function in mice developing type 2 diabetes. The longitudinal changes in retinal neuronal function and blood flow responses to a 10-min systemic hyperoxia and a 3-min flicker stimulation were evaluated every 2 weeks in diabetic db/db mice and nondiabetic controls (db/m) from age 8 to 20 weeks. The retinal blood flow and neural activity were assessed using laser speckle flowgraphy and electroretinography (ERG), respectively. The db/db mice had significantly higher blood glucose levels and body weight. The resting retinal blood flow was steady and comparable between two groups throughout the study. Hyperoxia elicited a consistent decrease, and flicker light an increase, in retinal blood flow in db/m mice independent of age. However, these flow responses were significantly diminished in db/db mice at 8 weeks old and then the mice became unresponsive to stimulations at 12 weeks. Subsequently, the ERG implicit time for oscillatory potential was significantly increased at 14 weeks of age while the a-wave and b-wave amplitudes and implicit times remained unchanged. The deficiencies of flow regulation and neurovascular coupling in the retina appear to precede neural dysfunction in the mouse with type 2 diabetes.

Role of ICAM-1 in impaired retinal circulation in rhegmatogenous retinal detachment.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r = - 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = - 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

Development of Stage 4 Macular Hole after Spontaneous Closure in a Patient with Stage 2 Macular Hole and a Lamellar Macular Hole-Associated Epiretinal Proliferation.

Herein, we report the longitudinal observation of a case with reopening of the macular hole associated with a lamellar macular hole-associated epiretinal proliferation (LHEP) followed by spontaneous closure in patients with stage 2 idiopathic macular hole. A 64-year-old woman was referred for the decreased visual acuity (VA) and acute anorthopia in the right eye. Funduscopy and optical coherence tomography (OCT) showed stage 2 full-thickness macular hole without posterior vitreous detachment (PVD) and operculum formation. Her best-corrected visual acuity (BCVA) was 20/32. One month later, the diameter of the macular hole was getting small and VA improved. Six months later, the macular hole was treated spontaneously with the attached hyaloid membrane to the macula by OCT and the BCVA improved to 20/20. Fourteen months after the first visit, the BCVA decreased to 20/50 and the patient was diagnosed with stage 4 macular hole with complete PVD. OCT showed full-thickness macular hole with a LHEP in the right eye. After 25G-gauge vitrectomy with the peeling of internal limiting membrane (ILM) and LHEP, the macular hole was closed and BCVA finally improved to 20/25. Spontaneous macular hole closure without PVD may rarely occur in patients with LHEP. The surgical removal of ILM and LHEP may contribute to the successful macular hole closure after vitrectomy.

The kebab technique uses a bipolar pencil to retrieve a dropped nucleus of the lens via a small incision.

We developed a new method to retrieve a dropped nucleus of the lens via a small incision using bipolar pencils, the kebab technique, to solve the lack of small-gauge fragmatomes, and the expense and toxicity of perfluorocarbon liquids (PFCL). A total of 8 eyes in 6 patients underwent this technique and were reviewed. After vitrectomy, the dropped nucleus of the lens was lifted from the retina by adhesion with a bipolar pencil, and phacoemulsification was performed while rotating the lens. The outcome measures were best-corrected visual acuity (BCVA), intraocular pressure (IOP), and corneal endothelial cell density before and after surgery. Surgical indications included zonular weakness, trauma, acute angle closure attack, and phacolytic glaucoma. At 1 month, BCVA improved from a mean (standard deviation, SD) 1.67 logMAR (0.90) to 1.14 logMAR (1.01). The mean preoperative IOP was 24.5 (16.8) mmHg and postoperative IOP was 11.0 (2.8) mmHg. The mean preoperative corneal endothelial cell count was 2600 (322) cells/mm2 (one eye was unmeasurable) and postoperative corneal endothelial cell count was 2387 (431) cells/mm2. There were no postoperative complications. The retrieval of a dropped nucleus of the lens using a bipolar pencil enables small incisions without using PFCL.

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial.

PURPOSE: To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). STUDY DESIGN: Prospective, open-label, multicenter, single-arm, nonblinded clinical study. METHODS: Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. RESULTS: Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P < .001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P = .782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (- 4.3 ± 9.2 letters) at 1 year (P < .001). Treatment intervals were extended to 12 and 16 weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. CONCLUSIONS: The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16 weeks is a realizable rational strategy for DME treatment over 1 year.