Asia-Pacific Technology and Trend Survey 2016-2017.

PURPOSE: To report the results of a survey conducted among retina specialists in the Asia-Pacific region on real-life practice patterns in the management of vitreoretinal diseases. DESIGN: Prospective questionnaire-based study. METHODS: In 2016 and 2017, a link was sent to 1400 retinal specialists across the Asia-Pacific region by e-mail, which directed to a web-based questionnaire (Google forms or Survey Monkey) with secure confidential access. Answers to some of the common questions were compared with the domestic and global trends results of the 2016 American Society of Retina Specialists Preferences and Trends survey. RESULTS: Of 1400 retinal specialists who received the email broadcast, 539 (38.5%) and 200 (14.3%) completed the survey in 2016 and 2017, respectively. Among those who completed the survey, approximately 85% practiced combined medical and surgical retina. In the management of wet age-related macular degeneration, ranibizumab was the drug of choice (41% of respondents) in 2016, and bevacizumab (48%) in 2017. In the management of polypoidal choroidal vasculopathy, both combination of verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF) (59% of respondents) and intravitreal aflibercept monotherapy (53%) were preferred. Anti-VEGF treatment remained the first choice for center-involving diabetic macular edema (DME) (78% in 2016 and 87% in 2017) and switching to dexamethasone implant in nonresponding DME was preferred after 6 anti-VEGF injections (42% in 2016 and 53% in 2017). CONCLUSIONS: The survey revealed information that may be close to real-world practices in the Asia-Pacific region and could be of help to understand the transformation of global trends and practices due to evolving evidence and technologies.

Optical coherence tomography predicts visual outcome in acute central retinal vein occlusion.

PURPOSE: To investigate the clinical features of central retinal vein occlusion (CRVO) in relation to the presence of a prominent middle limiting membrane (p-MLM) sign on presenting optical coherence tomography, which may suggest macular ischemia and poor visual outcome. METHODS: Fifty consecutive eyes with acute CRVO of <1 month of symptom duration before presentation were retrospectively reviewed. A hyperreflective line located in the outer plexiform layer (p-MLM) in optical coherence tomography was used as a sign of acute ischemia. Cases with p-MLM were grouped and compared with the group of eyes with no p-MLM sign (non-MLM group) for clinical features including visual acuities, central fovea thickness, and CRVO types. RESULTS: Among the 50 eyes, 14 (28%) eyes showed a p-MLM sign, 21 (42%) eyes did not, and others had equivocal findings. Eyes with p-MLM sign presented worse initial and final best-corrected visual acuity compared with the non-MLM group (1.10 ± 0.72 vs. 0.47 ± 0.49 logMAR in the initial best-corrected visual acuity, P = 0.007; and 1.08 ± 0.86 vs. 0.32 ± 0.41 logMAR in the final best-corrected visual acuity, P = 0.044) in patients with a follow-up duration of 6 months or longer. The p-MLM group eyes showed a higher tendency toward being classified as ischemic type CRVO (57.1 vs. 4.8%, P = 0.001). CONCLUSION: Central retinal vein occlusion showing p-MLM on optical coherence tomography had worse visual outcome with higher incidence of being classified into ischemic type CRVO.

Subretinal tenecteplase injection in a submacular hemorrhage from polypoidal choroidal vasculopathy: a case report.

PURPOSE: The purpose of this report was to describe a case with a thick submacular hemorrhage (SMH) resulting from polypoidal choroidal vasculopathy that was successfully treated with a subretinal tenecteplase injection. METHODS: A retrospective case report. RESULTS: A 63-year-old man with acute SMH secondary to polypoidal choroidal vasculopathy underwent a partial posterior vitrectomy, a subretinal tenecteplase (100 µg/0.1 mL) injection with air/fluid exchange, and an intravitreal injection of bevacizumab (2.5 mg/0.1 mL). His preoperative corrected visual acuity was 20/30, but the SMH threatened the fovea. The SMH was displaced inferiorly and absorbed completely at 1 month postoperative. His visual acuity decreased to 20/40 1 week postoperative but recovered to 20/20 2 months after surgery. The electroretinogram showed no distinct elongation of implicit time and slightly decreased amplitude of a-wave and b-wave at 3 months postoperative; optical coherence tomography presented disruption of the inner segment/outer segment line at the onset of SMH but recovered completely at 3 months postoperative. CONCLUSION: Subretinal tenecteplase was found to have sufficient hemolytic function and no retinal toxicity and could represent a feasible treatment option for the management of SMH.

Polyunsaturated Fatty Acid Composition of Surgically Removed Hard Exudates in Diabetic Macular Edema.

Three eyes of 2 patients with diabetic macular edema underwent a vitrectomy to remove subfoveal hard exudates. Fatty acid compositions of hard exudates and plasma phospholipids (PL) as an objective estimation of dietary intake were analyzed. Polyunsaturated fatty acids (PUFA) were relatively consistent in hard exudates and PL, but were less abundant in hard exudates. The hard exudates had lower levels of eicosapentaenoic acid (EPA, C20:5 omega3) and docosahexaenoic acid (DHA, C22:6 omega3), which oxidized more readily than other PUFA. Dietary PUFA may be associated with the composition of retinal hard exudates.

Lensectomy using a bimanual microincision cataract surgery technique during pars plana vitrectomy.

Lens extraction during vitrectomy is sometimes necessary to obtain an adequate view of the retina. Currently, phacoemulsification through a clear corneal incision with implantation of a foldable intraocular lens has become the preferred technique for cataract extraction during pars plana vitrectomy. The authors described the technique of lensectomy using a bimanual microincisional cataract surgery technique during pars plana vitrectomy and insertion of the intraocular lens at the end of surgery, which has several advantages over conventional coaxial phacoemulsification procedures.

Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide).

BACKGROUND: To evaluate the efficacy of timolol-dorzolamide drops used to decrease aqueous outflow from the eye on the prolongation of the biological activity of intravitreal bevacizumab. METHODS: Thirty-eight eyes of 38 patients with macular edema (ME) following retinal vein obstruction (RVO) were enrolled. These patients were randomly assigned into 2 groups: timolol-dorzolamide drops twice daily (n = 19) or no eyedrops (control; n = 19). All patients received 1.25 mg (in 0.05 mL) of bevacizumab intravitreally and were examined before treatment, 1 week after injection, and then every 4 weeks after injection. For each patient, visual acuity (VA), intraocular pressure (IOP), and central retinal thickness (CRT) by optical coherence tomography (OCT) were recorded before injection and at each visit after injection. The mean CRT at each timepoint was considered to directly reflect the biological activities of bevacizumab at those times. RESULTS: The mean CRT measured by OCT showed a significant decrease 1 week after treatment in both groups, and this difference was maintained for a total of 9 weeks (paired t-test, <0.001). The mean CRT at 1 week post-injection showed no significant between-group difference (p = 0.781). At 5 weeks post-injection, the timolol-dorzolamide group showed a significantly smaller mean CRT than the control group (p = 0.032). The difference in mean CRT between the 2 groups disappeared, however, at 9 weeks post-injection (p = 0.462). In both groups, VA improved significantly 1 week after injection, and these changes were maintained to 9 weeks post-injection in both groups. The mean VA of the 2 groups showed no difference at any time. CONCLUSIONS: Timolol-dorzolamide aqueous depressant drops may delay the elimination of intravitreal bevacizumab but clinical efficacy of the eyedrops have not been proven in this study.

Low doses of cannabinoids enhance the antinociceptive effects of intracisternally administered mGluRs groups II and III agonists in formalin-induced TMJ nociception in rats.

This study provides the first demonstration that central cannabinoids modulate the antinociceptive actions of metabotropic glutamate receptors (mGluRs) on formalin-induced temporomandibular joint (TMJ) nociception. Noxious scratching behavior induced by formalin injection in the TMJ was used as a model of pain. Intracisternal injection of 30mug of WIN 55,212-2, a non-subtype selective cannabinoid receptor agonist, attenuated the number of scratches by 75% as compared with the vehicle-treated group, whereas vehicle alone or 3 or 10 microg of WIN 55,212-2 had no effect. To explore the postulated interaction between central cannabinoid receptors and mGluRs, effects of combined administration of sub-analgesic doses of WIN 55,212-2 and group II or III mGluR agonists were tested. Group II or III mGluRs agonists were administered intracisternally 10 min after intracisternal administration of WIN 55,212-2. Neither 100 nmol APDC, a group II mGluRs agonist, nor L-AP4, a group III mGluR agonist, altered nociceptive behavior when given alone but significantly inhibited the formalin-induced nociceptive behavior in the presence of a sub-threshold dose ( 3microg) of WIN 55,212-2. The ED50 value of APDC or L-AP4 was significantly reduced upon co-treatment with WIN 55,212-2 than in the vehicle-treated group, highlighting the important therapeutic potential of the combined administration of group II or III mGluR agonists with cannabinoids to effectively treat inflammatory pain associated with the TMJ. Potentiating effects of group II or III mGluRs agonists will likely permit the administration of cannabinoids at doses that do not achieve significant accumulation to produce undesirable motor dysfunction.

Wound leakage and hypotony after 25-gauge sutureless vitrectomy: factors affecting postoperative intraocular pressure.

BACKGROUND AND OBJECTIVE: To investigate the factors related to postoperative hypotony after 25-gauge sutureless vitrectomy. PATIENTS AND METHODS: Of 109 consecutive eyes undergoing sutureless vitrectomy, 95 fluid-filled eyes were randomly assigned to three groups according to the order of infusion cannula removal. In group 1 (30 eyes), the infusion was removed first. In group 2 (32 eyes), the infusion was removed after another cannula. In group 3 (33 eyes), the infusion was removed last. Intraocular pressure (IOP) was measured on preoperative day 1 and postoperative days 1, 7, and 30. RESULTS: Mean age was 58.9 +/- 11.6 years (range: 18 to 80 years). Among each factor (including order of infusion removal, age, sex, axial length, preoperative IOP, previous vitrectomy, indications for vitrectomy and lens status), only age was significantly correlated with IOP on postoperative day 1 (P = .019). In 13 eyes in which hypotony persisted through postoperative day 2 (IOP < or = 5 mm Hg), the age of the patients was significantly younger than those who did not experience persisting hypotony (P = .006). CONCLUSION: Younger patients were more likely to experience early postoperative hypotony.

Short-term results of intravitreal bevacizumab for macular edema with retinal vein obstruction and diabetic macular edema.

OBJECTIVE: The aim of this study was to identify the short-term effect, safety, and durability of intravitreally injected bevacizumab in patients with macular edema (ME) caused by retinal vein obstruction (RVO) and diabetic macular edema (DME). METHODS: We retrospectively evaluated 39 eyes of 36 patients, 14 with ME caused by RVO and 25 with DME, who received intravitreal bevacizumab (1.25 mg) and were followed up for at least 3 months. Monthly assessments examined safety, best corrected visual acuity with an ETDRS chart (logMAR), and central retinal thickness (CRT) using optical coherence tomography. RESULTS: No significant ocular or systemic side-effects were observed. The follow-up period was 5.4 +/- 1.1 months (mean +/- standard deviation). During follow-up, the mean number of injections was 1.4 +/- 0.5. The baseline mean logMAR was 0.91 +/- 0.51, and the mean CRT was 552.6 +/- 186.7 microm. At 1, 2, and 3 months, the mean logMAR was 0.67 +/- 0.46 (paired t test, P < 0.001), 0.66 +/- 0.46 (P < 0.001), and 0.69 +/- 0.45 (P < 0.001), respectively, and the mean CRT was 323.1 +/- 151.9 mum (P < 0.001), 324.6 +/- 136.9 mum (P < 0.001), and 382.5 +/- 130.4 microm (P < 0.001), respectively. Fourteen (14) of 34 eyes with more than 3 months of follow-up required a second injection at a mean 3.4 +/- 1.0 months after the initial injection. For both ME caused RVO and DME patients, a bevacizumab administration improved logMAR and CRT at each time point through to 6 months, except for logMAR in DME at 1 week (P = 0.081), 5 months (P = 0.130) and 6 months (P = 0.759). CONCLUSIONS: An intravitreal bevacizumab injection for ME caused by RVO and DME was safe and effective for improving visual acuity and reducing CRT.

Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats.

Microinjection of formalin (5%, 50 microl) into a temporomandibular joint (TMJ) causes noxious behavioral responses in freely moving rats. In the present study, we investigated the role of central cyclooxygenase (COX) pathways in IL-1beta-induced hyperalgesia with formalin-induced TMJ pain model. Intra-articular injection of 100 pg or 1 ng of IL-1beta significantly facilitated formalin-induced behavior by 130 or 174% in the number of scratches. Intracisternal administration of 100 pg or 1 ng of IL-1beta also significantly increased formalin-induced behavior by 166 or 82% in the number of scratches. IL-1beta-induced hyperalgesia was blocked by pretreatment with IL-1 receptor antagonist. Intracisternal pretreatment with SC-560, a selective COX-1 inhibitor, or NS-398, a selective COX-2 inhibitor, abolished intra-articular administration of IL-1beta-induced hyperalgesic response. Intracisternal pretreatment with NS-398, a selective COX-2 inhibitor, abolished the intracisternal administration of IL-1beta-induced hyperalgesic response, while pretreatment with SC-560, a selective COX-1 inhibitor, did not change IL-1beta-induced hyperalgesic responses. On the other hand, pretreatment with acetaminophen, a tentative COX-3 inhibitor, also abolished both intra-articular and intracisternal administration of IL-1beta-induced hyperalgesic responses. These results indicate that central COX-2 plays important role in the central administration of IL-1beta-induced hyperalgesia and that central COX-1/2 pathways mediate peripheral administration of IL-1beta-induced hyperalgesia in the TMJ. Central COX-3 inhibitor seems to play an important role in the nociceptive process associated with both peripheral and central administration of IL-1beta-induced hyperalgesia in TMJ. It is concluded that central acting of COX-3 inhibitors may be of therapeutic value in the treatment of inflammatory pain in TMJ.

Retinal toxicity of commercial tissue plasminogen activator is mediated by the induction of nitric oxide in the mouse retinal primary cells.

PURPOSE: Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing L-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO). METHODS: Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent. RESULTS: tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. L-arginine seems to be the major factor in retinal toxicity of commercial tPA (containing L-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing L-arginine) or L-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or L-arginine. CONCLUSIONS: This study suggests that l-arginine from commercial tPA (containing L-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.

The effect of photodynamic therapy with rose bengal on posterior capsule opacification in rabbit eyes.

We investigated the in vivo effect of photodynamic therapy (PDT) using rose bengal on the development of posterior capsule opacification (PCO). Endocapsular phacoemulsification was performed on white rabbits, which were divided into 4 groups: control group; group 1, treated with visible light only; group 2, treated with rose bengal only, and group 3, treated with PDT. In the case of the PDT group, rose bengal dissolved in sodium hyaluronate was injected into the empty capsular bag and treated with visible light. Three months after surgery, the rabbits were sacrificed and the eyeballs enucleated. The obstruction rate of visible light caused by PCO was measured with an optical powermeter. The mean obstruction rate was 30.6% in the control group, 28.3% in group 1, 19.3% in group 2, and 14.3% in group 3. Group 3 showed a statistically significant decrease in PCO compared with the control group and group 1 (p = 0.0014). Our results suggest that PDT using rose bengal effectively decreased PCO in rabbit eyes.

Visual field defect caused by nerve fiber layer damage associated with an internal limiting lamina defect after uneventful epiretinal membrane surgery.

PURPOSE: To report a case of visual field defect caused by damage of the nerve fiber layer associated with an internal limiting lamina defect after uneventful epiretinal membrane peeling. DESIGN: Interventional case report. METHODS: In the right eye, a 43-year-old male patient developed a nasal step and mild inferior arcuate scotoma after uneventful epiretinal membrane surgery without any associated glaucoma. Transmission electron microscopy was performed on the epiretinal membrane specimens. RESULTS: An epiretinal membrane specimen showed adhesion between epiretinal membrane and axons of nerve fiber layer in the area of the internal limiting lamina defect. CONCLUSION: Adhesion between epiretinal membrane and retinal tissue in the area of the internal limiting lamina defect may cause damage of the nerve fiber layer and visual field defect after epiretinal membrane peeling.