ADVERSE EFFECT OF MACULAR INTRARETINAL HEMORRHAGE ON THE PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE.

PURPOSE: To investigate the clinical course of submacular hemorrhage associated with ruptured retinal arterial macroaneurysm using swept-source optical coherence tomography. METHODS: This study included 23 eyes of 23 consecutive patients diagnosed with submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. Cases underwent displacement of submacular hemorrhage (vitrectomy + subretinal injection of tissue plasminogen activator + air tamponade) and were followed up for 6 months after surgery. Localization of the preoperative hemorrhage and its effect on preoperative and postoperative best-corrected visual acuity, central retinal thickness, and continuity of the ellipsoid zone were measured. RESULTS: Macular intraretinal hemorrhage (IRH) was observed in 17 eyes (73.9%, IRH [+] group) and was not observed in 6 eyes (26.1%, IRH [-] group). The IRH (+) group showed worse postoperative best-corrected visual acuity values compared with the IRH (-) group (0.89 ± 0.47 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/155 and 0.16 ± 0.23, 20/29, respectively; P < 0.01), smaller central retinal thickness values (97.7 ± 53.5 µm, 173.0 ± 32.3 µm, respectively; P < 0.01), and a higher rate of ellipsoid zone disruption (100%, 33.3%, respectively; P < 0.01). CONCLUSION: Patients with preoperative macular IRH showed lower postoperative visual acuity and worse macular contour after submacular hemorrhage displacement compared with patients without macular IRH.

EN FACE IMAGE-BASED ANALYSIS OF RETINAL TRACTION CAUSED BY EPIRETINAL MEMBRANE AND ITS RELATIONSHIP WITH VISUAL FUNCTIONS.

PURPOSE: To evaluate the relationship between retinal traction caused by epiretinal membrane and visual functions. METHODS: In this institutional study, en face swept-source optical coherence tomography images of 141 eyes of 130 patients with epiretinal membrane were analyzed to investigate maximum depth of retinal folds, which represents retinal traction strength and the distribution pattern of retinal folds. We investigated the relationships between the maximum depth and distribution pattern of retinal folds and visual functions as well as the effects of membrane peeling. RESULTS: Maximum retinal fold depth was significantly correlated with the metamorphopsia score (P < 0.001). Fifteen eyes showed retinal folds radially extending from the macular epiretinal membrane (radiating folds group), whereas 126 eyes showed a multidirectional pattern of retinal folds (multidirectional folds group). The radiating folds group showed a significantly lower metamorphopsia score (P = 0.014). Multiple regression analysis revealed that the metamorphopsia score was significantly related to maximum retinal fold depth (P = 0.003), distribution pattern (P = 0.015), and central retinal thickness (P < 0.001). One month after membrane peeling, parafoveal retinal folds resolved completely in all cases, and both visual acuity (P < 0.001) and average metamorphopsia score (P = 0.036) were significantly improved. CONCLUSION: Both the strength and the distribution pattern of retinal traction are significantly related to metamorphopsia in epiretinal membrane patients.

RELATIONSHIP BETWEEN PREOPERATIVE FOVEAL MICROSTRUCTURE AND VISUAL ACUITY IN MACULA-OFF RHEGMATOGENOUS RETINAL DETACHMENT: Imaging Analysis by Swept Source Optical Coherence Tomography.

PURPOSE: To visualize foveal microstructures in macula-off rhegmatogenous retinal detachment using swept source optical coherence tomography preoperatively and postoperatively and to investigate the relationship between foveal microstructures and postoperative visual acuity. METHODS: We retrospectively analyzed 42 eyes of 42 consecutive patients diagnosed with macula-off rhegmatogenous retinal detachment who underwent anatomically successful repair surgery and were followed up for 6 months. We used swept source optical coherence tomography to investigate the relationship between preoperative and postoperative continuity of both the external limiting membrane (ELM) and ellipsoid zone (Ez) and preoperative and postoperative best-corrected visual acuity. RESULTS: Both preoperative ELM and Ez were continuous in 9 eyes (21%; ELM+/Ez+ eyes), only the ELM was continuous in 25 eyes (60%; ELM+/Ez- eyes), and neither was continuous in 8 eyes (19%; ELM-/Ez- eyes). Postoperative best-corrected visual acuity in ELM+/Ez+ eyes (-0.05 ± 0.04 logarithm of the minimum angle of resolution units, Snellen equivalent 20/18) was significantly better than that in both ELM+/Ez- (0.16 ± 0.16, 20/29; P = 0.03) and ELM-/Ez- (0.86 ± 0.37, 20/145; P < 0.001) eyes. Postoperative best-corrected visual acuity was significantly better in ELM+/Ez- than in ELM-/Ez- eyes (P < 0.001). CONCLUSION: In macula-off rhegmatogenous retinal detachment, preoperative continuity of the ELM and Ez may be a predictor of postoperative best-corrected visual acuity.

Two-year Results of Intravitreal Ranibizumab Injections Using a Treat-and-extend Regimen for Macular Edema due to Branch Retinal Vein Occlusion.

We investigated the effectiveness of a treat-and-extend regimen (TAE) of intravitreal ranibizumab injections for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively examined 2-year results of 32 eyes of 32 patients who underwent TAE to treat ME due to BRVO. The patients whose treatment interval extended to ≥ 12 weeks were switched to a pro re nata regimen (PRN). For the patients whose treatment interval was <12 weeks, TAE was continued. At 2 years, 10 eyes had required no additional injections after the initial treatment period [recurrence(-) group], whereas the other 22 eyes required additional treatment [recurrence(+) group]. Among the recurrence(+) patients, 11 eyes (34.4% of total) were eventually switched from TAE to PRN; the other 11 eyes (34.4%) continued TAE for 2 years. Visual acuity and central retinal thickness were significantly improved in both the recurrence(+) and (-) groups, and there was no significant betweengroup difference in visual acuity at 2 years. Univariate analyses revealed significant differences in visual acuity (p=0.004), age (p=0.014), and vessel occlusion site (p=0.018) between these groups. Our results suggest that TAE may be effective for BRVO patients with lower visual acuity, older age, and occlusion of a major vein.

Embedding of lamellar hole-associated epiretinal proliferation combined with internal limiting membrane inversion for the treatment of lamellar macular hole: a case report.

BACKGROUND: We recently reported that lamellar macular hole (LMH) with lamellar hole-associated epiretinal proliferation (LHEP) can be effectively treated by embedding the LHEP into the retinal cleavage to improve foveal contour and visual acuity. Here, we report a case of LMH with LHEP for which we performed embedding of the LHEP combined with internal limiting membrane (ILM) inversion. We then evaluated the effects of this surgery on macular morphology and visual functions. CASE PRESENTATION: A 62-year-old man presented with visual disturbance (20/29) and metamorphopsia in his right eye. B-scan optical coherence tomography (OCT) imaging revealed the presence of both partial-thickness defect of the macula with degenerative retinal cleavage and LHEP at the surface of the retina. En face OCT imaging showed the absence of retinal fold. We performed phacoemulsification with intraocular lens implantation, vitrectomy, embedding of LHEP into the retinal cleavage, and ILM inversion. Three months after the surgery, both foveal contour and visual acuity (20/20) were improved and metamorphopsia was reduced. CONCLUSION: Embedding of the LHEP combined with ILM inversion may be an effective treatment for LMH with LHEP.

Successful resolution of coats disease by photodynamic therapy: a case report.

BACKGROUND: Coats disease is a retinal disease characterized by exudative retinal detachment due to abnormal retinal blood vessels. Coats disease is generally treated using laser photocoagulation and cryotherapy to ablate the abnormal retinal blood vessels. However, if abnormal blood vessels are present near the posterior pole of the eye and there is a severe exudative change there, it is difficult to perform these standard treatments. We describe a case of Coats disease with severe exudative retinal change and retinal vascular abnormality near the posterior pole for which we performed photodynamic therapy and successfully suppressed the disease and improved vision. CASE PRESENTATION: A 15-year-old Japanese boy presented to hospital with a chief complaint of decreased vision in his right eye. At the initial examination, corrected visual acuity of the right eye was 20/100. On the right fundus, exudative retinal detachment with subretinal haemorrhage was observed from the upper intermediate periphery to the posterior pole. Abnormal telangiectatic vessels and microaneurysms were found at the nasal peripheral retina. From these findings, we diagnosed the case as Coats disease. We conducted photodynamic therapy for the right eye. At 10 months after treatment, both the subretinal haemorrhage and the exudative retinal detachment had disappeared completely. Further, the retinal structure of the macula had recovered, and right vision had improved to 20/20. CONCLUSION: Photodynamic therapy may be an effective and safe treatment for Coats disease in cases that present with abnormal retinal vessels close to the posterior pole of the eye.

Impact of Polyp Regression on 2-year Outcomes of Intravitreal Aflibercept Injections: A Treat-and-Extend Regimen for Polypoidal Choroidal Vasculopathy.

We conducted intravitreal aflibercept injections (IVAs) for 37 Japanese patients (28 males, 9 females, mean age 73.4 years) with polypoidal choroidal vasculopathy (PCV), with a treat-and-extend regimen (TER). We evaluated the impact of polyp regression after a loading dose (2-mg IVA 1×/month for 3 months) on the patients' 2-year treatment outcomes. Thirty-seven eyes were treated with IVA by a TER for 2 years. We divided the patients into 2 groups based on their polyp status after the loading dose: polyp regression (PR+) (n=19) and no polyp regression (PR-) (n=18). We compared the groups' best-corrected visual acuity (BCVA), central retinal thickness (CRT), recurrence rate, total number of injections, and final treatment interval. Both the BCVA and CRT were significantly improved by the treatment in both groups, with no between-group difference in the amount of change (p=0.769). In the polyp regression (+) group, recurrence was significantly less common (p=0.03), the mean total number of injections was significantly lower (p=0.013), and the mean treatment interval was significantly longer (0.042). Regarding the 2-year outcomes for PCV, the eyes with post-loading-dose polyp regression demonstrated less frequent recurrence and required fewer numbers of injections compared to the eyes without polyp regression.

Results of a Treat-and-Eextend Regimen of Intravitreal Ranibizumab Injection for Macular Edema due to Branch Retinal Vein Occlusion.

To investigate the effectiveness of a treat-and-extend regimen (TAE) of intravitreal ranibizumab injections (IVR) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively examined 35 eyes of 35 patients with ME due to BRVO who underwent TAE for 1 year. Patients whose treatment interval extended to 12 weeks were switched to a pro re nata regimen (PRN; TAE to PRN group), while TAE was continued for patients whose treatment interval was less than 12 weeks (continued TAE group). Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and predictive factors for inclusion in the TAE to PRN group were analyzed. BCVA and CRT both improved significantly at 1 year compared with baseline (p<0.001). Sixteen eyes (45.7%) were included in the TAE to PRN group, while 19 eyes (54.3%) were included in the continued TAE group. BCVA in the TAE to PRN group was significantly better than that in the continued TAE group at 1 year (p=0.047). BCVA at baseline and macular BRVO were significant predictive factors for inclusion in the TAE to PRN group. TAE was effective for improving BCVA and CRT. The TAE to PRN group showed significantly better prognosis.

Efficacy of vitrectomy and inner limiting membrane peeling in age-related macular degeneration resistant to anti-vascular endothelial growth factor therapy, with vitreomacular traction or epiretinal membrane.

PURPOSE: We assessed the efficacy of vitrectomy and inner limiting membrane (ILM) peeling, followed by anti-vascular endothelial growth factor (VEGF) therapy, anti-VEGF-resistant age-related macular degeneration (AMD) due to vitreomacular traction (VMT) or epiretinal membrane (ERM). METHODS: We identified six patients with anti-VEGF-resistant AMD due to VMT or ERM amongst a total of 588 patients with AMD (821 eyes) referred to Okayama University Hospital between February 2012 and May 2014. These patients underwent vitrectomy to release the VMT (4 cases) or remove the ERM (2 cases), along with ILM peeling. The regimen used for intravitreal injections of anti-VEGF reagents after surgery was based on the severity of exudative changes in each patient. Preoperative and postoperative best-corrected visual acuity (BCVA) and central retinal thickness (CRT) measurements were compared. RESULTS: After vitrectomy and ILM peeling, all six patients responded to anti-VEGF therapy, which was then able to maintain dry retinas. Mean BCVA did not improve significantly (0.49 ± 0.28 before vs. 0.43 ± 0.38 after surgery, P = 0.538). However, mean CR was significantly decreased after surgery, from 423 ± 83.5 µm to 257 ± 75.8 µm (P = 0.0078). CONCLUSIONS: Vitrectomy and ILM peeling followed by anti-VEGF therapy may be a useful therapeutic option for anti-VEGF-resistant AMD with VMT or ERM.

COMPARISON OF HALVING THE IRRADIATION TIME OR THE VERTEPORFIN DOSE IN PHOTODYNAMIC THERAPY FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the efficacy and safety of photodynamic therapy using reduced irradiation time or reduced verteporfin dose for chronic central serous chorioretinopathy. METHODS: Between April 2011 and December 2013, 45 eyes with chronic central serous chorioretinopathy (43 consecutive patients) were treated with photodynamic therapy, using either half the irradiation time (18 eyes) or half the verteporfin dose (27 eyes). Outcome measures at follow-up, over at least 3 months, were complete resolution of serous retinal detachment, best-corrected visual acuity, and central retinal thickness. RESULTS: After 3 months, serous retinal detachment had completely resolved in 88.8% of eyes in both treatment groups, which were therefore not significantly different. The logarithm of the minimal angle of resolution best-corrected visual acuity (Snellen equivalent) improved from 0.245 (20/35) to 0.130 (20/27) (P < 0.05, paired t-test) in the reduced time group and from 0.283 (20/38) to 0.138 (20/27) (P < 0.05) in the reduced verteporfin group. Final best-corrected visual acuities in the 2 groups were not significantly different. Central retinal thicknesses dropped from 337.0 µm to 146.6 µm (P < 0.05) in the reduced time group and from 343.5 µm to 166.9 µm (P < 0.05) in the reduced verteporfin group. No ocular or systemic side effects were observed. CONCLUSION: Reduced irradiation time and reduced verteporfin dose were equally effective and safe in photodynamic therapy for chronic central serous chorioretinopathy.

Successful displacement of a traumatic submacular hemorrhage in a 13-year-old boy treated by vitrectomy, subretinal injection of tissue plasminogen activator and intravitreal air tamponade: a case report.

BACKGROUND: The natural course of submacular hemorrhage resulting from traumatic choroidal rupture generally has a poor outcome unless treated. The intravitreal injection of gas only or gas with recombinant tissue plasminogen activator (rt-PA) has been reported to be effective, but has also been reported to induce severe complications such as retinal detachment and vitreous hemorrhage. Recently, we reported a safe and effective procedure for treating submacular hemorrhage due to polypoidal choroidal vasculopathy (PCV) with a low dose of rt-PA. Here we report the application of this procedure to a case of traumatic submacular hemorrhage in a 13-year-old boy, which achieved a good visual outcome. CASE PRESENTATION: A 13-year-old Japanese boy presented with a thick submacular hemorrhage in his left eye as a result of blunt trauma from being hit by a sinker. Best-corrected visual acuity (BCVA) was assessed as only able to perceive hand motions. We carried out a vitrectomy, subretinal injection of 4,000 IU rt-PA (6.9 µg) and air tamponade. The day after surgery, most of the submacular hemorrhage had moved to the inferior periphery. One month after the surgery, we observed cataract formation, thin remnants of the submacular hemorrhage and juxtafoveal choroidal rupture. We carried out cataract surgery and injected bevacizumab intravitreally to prevent the development of choroidal neovascularization. Two months after the second surgery, the submacular hemorrhage had totally disappeared and the patient had a BCVA of 20/40. CONCLUSION: Vitrectomy, subretinal injection of rt-PA, and intravitreal air tamponade may be a promising strategy for treating traumatic submacular hemorrhage in young patients.

Case report: successful closure of a large macular hole secondary to uveitis using the inverted internal limiting membrane flap technique.

BACKGROUND: Macular holes (MHs) are one of the complications of posterior uveitis that can significantly disturb vision. Conventional MH surgery (vitrectomy, internal limiting membrane (ILM) peeling, and gas tamponade) has been reported to show lower closure rates in patients with MHs secondary to uveitis than in patients with idiopathic MHs. Recently, the inverted ILM flap technique has been reported to be effective for treating refractory MHs. Here, we describe the application of this technique in a patient with a large MH secondary to uveitis, and its successful closure. CASE PRESENTATION: An 80-year-old woman presented with a chronic, large MH secondary to uveitis. The minimum aperture diameter of the MH was 569 µm and extensive post-inflammatory chorioretinal atrophy was present, which included the juxtafoveal region. Vitrectomy with the inverted ILM flap technique assisted by low molecular weight hyaluronic acid was performed. Three days after surgery, the MH was closed successfully, without excessive gliosis. CONCLUSION: The inverted ILM flap technique may be the preferred surgical procedure for the treatment of large MHs secondary to uveitis.

POEMS syndrome in a 20-year-old patient diagnosed following a complaint of reduced visual acuity.

We report a case of POEMS syndrome in a 20-year-old patient diagnosed after visiting an eye clinic with a chief complaint of reduced visual acuity. A male university student aged 20 years was referred to our department complaining of blurred vision in both eyes that had persisted for 1 month. He also noted headache, nausea, and paresthesia in the lower extremities around the same time. The visual acuity of his right and left eye was 20/40 and 20/20, respectively. Optic disc edema and serous retinal detachment were present. Brain magnetic resonance imaging showed no intracranial abnormalities, while elevated cerebrospinal fluid pressure, reduced nerve conduction velocity in both lower extremities, hepatosplenomegaly, M proteinemia, high blood VEGF levels, osteoblastic and osteolytic changes in the spine, and atypical plasma cells in bone lesions were noted. From the above findings, the patient was diagnosed with POEMS syndrome. He received high-dose dexamethasone, thalidomide, and radiotherapy on the sacral mass, followed by high-dose melphalan with autologous stem-cell support, and showed subsequent systemic and ophthalmologic improvement. Here, we report the youngest case ever of POEMS syndrome with ocular manifestation. If patients have optic disc edema in both eyes with no intracranial space-occupying lesion, POEMS syndrome should be considered in differential diagnosis, regardless of age.

Interocular symmetry of the foveal avascular zone area in healthy eyes: a swept-source optical coherence tomography angiography study.

PURPOSE: To determine the presence or absence of interocular differences in the foveal avascular zone (FAZ) area in healthy eyes. STUDY DESIGN: Cross-sectional study. METHODS: We examined 236 healthy eyes of 118 consecutive subjects (mean age, 39.1 ± 18.9 years). We used swept-source optical coherence tomography angiography (OCTA) images of the FAZ to measure its area from both the superficial capillary plexus (SCP-FAZ) and the whole retinal capillary plexus (WCP-FAZ). We also investigated the relationship between interocular differences in SCP-FAZ and other factors such as: axial length, spherical equivalent, central retinal thickness, and retinal vascular density. RESULTS: There was no significant difference in the FAZ area between the right and left eyes in either the SCP-FAZ (P = 0.61) or WCP-FAZ (P = 0.80), and the FAZ areas of both eyes showed significant positive correlations (SCP-FAZ; P < 0.001, R2 = 0.884, WCP-FAZ; P < 0.001, R2 = 0.856). Bland-Altman plots showed that the mean interocular difference in SCP-FAZ area was 0.002 ± 0.037 mm2 (95% confidence interval, -0.072-0.075 mm2), and in the WCP-FAZ area, 0.050 ± 0.044 mm2 (95% confidence interval, -0.036-0.137 mm2). Multivariate regression analysis showed that none of the investigated factors were significantly associated with interocular differences in SCP-FAZ (P = 0.61, R2 = 0.138). CONCLUSIONS: There was no significant interocular difference in SCP- and WCP-FAZ areas in healthy eyes. The normal range of values for interocular difference in SCP-FAZ area was 0.002 ± 0.037 mm2 and in the WCP-FAZ area, 0.050 ± 0.044 mm2.

Outcomes of vitrectomy combined with subretinal tissue plasminogen activator injection for submacular hemorrhage associated with polypoidal choroidal vasculopathy.

PURPOSE: To examine the outcomes of vitrectomy with subretinal tissue plasminogen activator (tPA) injection and postoperative intravitreal antivascular endothelial growth factor (VEGF) injection for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Retrospective, consecutive case series. METHODS: Patients who underwent vitrectomy for SMH associated with PCV and who were followed up for at least 12 months were included. Surgery consisted of vitrectomy with subretinal tPA and air tamponade. Postoperative intravitreal anti-VEGF was administered pro re nata. The following were examined: best-corrected visual acuity (BCVA) at baseline, at 1 month, and at the final visit; the percentage of patients requiring anti-VEGF postoperatively; and the number of injections administered. RESULTS: This study included 23 eyes of 23 patients (21 men, 2 women) with a mean age of 72.5 ± 9.0 years. The mean duration from disease onset to surgery was 9.0 ± 6.6 days. The mean maximum SMH size was 5.8 ± 4.8 disc diameters. The mean follow-up period was 33 ± 14 months. The BCVA was significantly improved when compared with baseline 1 month after surgery and at the final visit. Postoperative anti-VEGF was required for 91% of the eyes. In eyes that underwent anti-VEGF therapy until the final visit, the mean injection number was 4.1/year. CONCLUSIONS: Vitrectomy with subretinal tPA and air tamponade improved visual acuity in patients with SMH associated with PCV. Postoperative intravitreal anti-VEGF injection maintained the improved BCVA throughout a mean period of 33 months.

Assessment of Lamellar Macular Hole and Macular Pseudohole With a Combination of En Face and Radial B-scan Optical Coherence Tomography Imaging.

PURPOSE: To investigate lamellar macular hole (LMH) and macular pseudohole (MPH) using a combination of en face and radial B-scan OCT. DESIGN: Retrospective observational case series. METHODS: Setting: Institutional study. PATIENT POPULATION: En face and radial B-scan OCT images of 63 eyes of 60 patients diagnosed with LMH or MPH based on an international classification were reviewed. OBSERVATION PROCEDURES: Cases were classified using en face images based on the presence/absence of epiretinal membrane (ERM), retinal folds, parafoveal epicenter of contractile ERM (PEC-ERM), and retinal cleavage. We compared the en face imaging-based classification system with the international classification system using radial B-scan images. We quantitatively evaluated visual function and macular morphology. MAIN OUTCOME MEASURES: Characterization of multimodal OCT-based subtypes of LMH and MPH. RESULTS: All cases showed ERM and were classified into 4 groups. In the first group, which lacked retinal folds and showed significantly lower visual acuity than the other groups, 81% of eyes had degenerative LMH. In the second group, which lacked PEC-ERM and retinal cleavage and showed significantly lower retinal fold depth, all eyes had MPH. The third group, in which 95% of eyes had symmetric tractional LMH, included eyes with retinal cleavage but without PEC-ERM, and this group showed higher circularity of the foveal aperture and cleavage area than the group with both these features, in which all eyes had asymmetric tractional LMH. CONCLUSIONS: Multimodal OCT enables classification of LMH and MPH based on pathologic conditions. Retinal traction in particular may be useful for determining treatment methods.

The influence of subretinal injection pressure on the microstructure of the monkey retina.

PURPOSE: To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. METHODS: After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. RESULTS: The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. CONCLUSIONS: The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

Retinal sensitivity after displacement of submacular hemorrhage due to polypoidal choroidal vasculopathy: effectiveness and safety of subretinal tissue plasminogen activator.

PURPOSE: To investigate the effectiveness of displacement of submacular hemorrhage (SMH) caused by polypoidal choroidal vasculopathy (PCV) by assessing retinal sensitivity using microperimetry. METHODS: We retrospectively reviewed the medical records of 11 consecutive PCV patients with SMH. All patients underwent vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-air exchange, followed by antivascular endothelial growth factor therapy using a pro re nata regimen. The retinal sensitivity was measured by use of microperimetry before and after surgery. RESULTS: The mean (SD) age of the patients was 74.1 ± 9.4 years. The mean SMH diameter was 6.8 ± 5.2 disc diameters. The best-corrected visual acuity (BCVA), mean retinal sensitivity, and mean number of measure points with a sensitivity ≥10 dB before the surgery were 0.94 ± 0.49, 4.2 ± 4.5 dB, and 15.6 ± 15.1 points, respectively. These had significantly improved 6 months after surgery (0.39 ± 0.37, 15.6 ± 7.3 dB, and 50.9 ± 22.2 points, respectively; P < 0.05 for all outcome measures). The mean number of measure points with an absolute scotoma before surgery had decreased significantly 6 months after surgery (from 40.5 ± 15.0 to 9.4 ± 16.0 points; P < 0.001). CONCLUSIONS: Displacement of SMH effectively improves retinal sensitivity as well as BCVA.

The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure.

Purpose: To investigate the mechanism of macular hole (MH) closure following the inverted internal limiting membrane (ILM) technique. Methods: We performed the inverted ILM flap surgical technique as an experimental MH model in monkeys, and investigated the process of MH closure immunohistochemically. We then investigated the effects of type IV collagen, fibronectin, and laminin, which are constituent proteins of the ILM, on the proliferation and migration of cultivated Müller cells (MIO-M1). We also investigated the expression of neurotrophic factors and basic fibroblast growth factor (bFGF) in human ILM and MIO-M1 cells, and the effect of MIO-M1 migration on the expression of these factors, via immunohistochemical staining and the real-time reverse transcription polymerase chain reaction. Results: Ten days after inverted ILM flap surgery, the MH had closed and proliferating glial fibrillary acidic protein (GFAP)-positive cells surrounded the ILM. Type IV collagen, fibronectin, and laminin all enhanced the proliferation of MIO-M1 cells, and type IV collagen and fibronectin enhanced the migration of MIO-M1 cells. Neurotrophic factors and bFGF were present on the surface of the human ILM, and MIO-M1 cells produced these factors. Neurotrophic factors and bFGF were expressed to a significantly greater extent by migrating MIO-M1 cells than by these cells in their static state. Conclusions: During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.