Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in Japanese patients with diabetic macular edema: 1-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME). STUDY DESIGN: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593). METHODS: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared. RESULTS: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified. CONCLUSION: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME.

Displacement of submacular hemorrhage secondary to age-related macular degeneration with subretinal injection of air and tissue plasminogen activator.

Submacular hemorrhage (SMH) can lead to devastating visual loss in patients with age-related macular degeneration. We retrospectively evaluated the surgical outcomes of vitrectomy with subretinal injection of tissue plasminogen activator, bevacizumab, and air in 13 cases. Visual prognosis, anatomical results obtained with optical coherence tomography (OCT), and their correlations were investigated. We analyzed OCT parameters including SMH height, pigment epithelial detachment (PED) height and width, and status of ellipsoid zone (EZ) line. Complete displacement of SMH was achieved in 12 eyes. At 3 months post-surgery, best-corrected visual acuity (BCVA) and SMH height exhibited significant improvements (P < 0.01). In eyes with preoperative SMH height < 300 µm and a detectable EZ line, BCVA was significantly improved at as early as 1 month, whereas the remaining eyes exhibited visual improvements only at 3 months. Postoperative BCVA positively correlated with preoperative BCVA (r = 0.86, P < 0.005), and negatively correlated with SMH size (r = 0.69, P < 0.01) and PED height (r = 0.58, P < 0.05) and width (r = 0.67, P < 0.05). Multivariate analyses confirmed preoperative BCVA as the predominant factor associated with postoperative BCVA (ß = 1.093, P < 0.05). In conclusion, significant improvements in BCVA and anatomical findings can be achieved with our reported surgical technique. Preoperative OCT findings may influence the duration required for visual improvements.

Long-term results of photodynamic therapy or ranibizumab for polypoidal choroidal vasculopathy in LAPTOP study.

BACKGROUND/AIM: We previously reported that ranibizumab performed better on visual prognosis than photodynamic therapy (PDT) in a Ranibizumab (Lucentis) And Photodynamic Therapy On Polypoidal choroidal vasculopathy (LAPTOP) study. To determine if the first-choice treatment, either PDT or intravitreal ranibizumab, has a long-term effect in patients with polypoidal choroidal vasculopathy (PCV). METHODS: We reviewed medical records of patientsrandomised to either PDT (29 eyes) or ranibizumab (27 eyes) from July 2009 to June 2011 in LAPTOP study. Retreatment or switching to other treatments were at the investigator's discretion after release from the 2-year LAPTOP study up to 5years. We evaluated visual acuity (VA), continuity of initial treatment, percentage of dry macula achievement and macular atrophy at 5 years. RESULTS: The logarithm of minimal angle of resolution VA was 0.56 in the PDT and 0.44 in the ranibizumab groups at baseline (p=0.101) and was 0.55 and 0.28 at 5years, respectively (p<0.05). More than 70% of the patients converted to aflibercept in following years. Achievement percentages of dry macula were 74% (PDT) and 63% (ranibizumab) at 5years, and macular atrophy was detected in 78% (PDT) and 60% (ranibizumab) with a mean area of 7.7 and 3.5 mm2, respectively (p=0.155). CONCLUSIONS: The better VA in the initial ranibizumab group compared with the PDT group at 2 years was retained at the 5-year follow-up.

Influences of 27-Gauge Vitrectomy on Corneal Topographic Conditions.

PURPOSE: To evaluate the influences of 27-gauge vitrectomy on corneal topographic conditions. METHOD: Fifty-six eyes of 56 patients undergoing 27-gauge vitrectomy were retrospectively studied. Twenty-three eyes with epiretinal membrane (ERM), 23 eyes with macular hole (MH), and 10 eyes with proliferative diabetic retinopathy (PDR) were included. Forty-five of the 56 eyes underwent 27-gauge phacovitrectomy (group 1), and the remaining 11 eyes underwent 27-gauge vitrectomy alone (group 2). Corneal topography was obtained with a wave-front analyzer preoperatively and at 1 and 3 months postoperatively. The corneal topographic parameters evaluated were the average corneal power, regular astigmatism, spherical aberration, and higher-order aberration (HOA). RESULTS: In between-group analyses of groups 1 and 2, no significant differences were observed regarding the changes of the 4 parameters from the baseline to 1 and 3 months postoperatively. No significant differences in the changes of all parameters from the baseline to 1 and 3 months postoperatively were also observed between MH group and the other two groups. A significant difference in the change of HOA from the baseline to 1 month postoperatively was observed between ERM and PDR group however, the difference disappeared at 3 months. CONCLUSION: 27-gauge vitrectomy did not induce substantial changes in the corneal topographic conditions.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS AND SURGICAL OUTCOMES OF TISSUE PLASMINOGEN ACTIVATOR-ASSISTED VITRECTOMY FOR SUBMACULAR HEMORRHAGE SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To study the relationship between morphologic findings using spectral domain optical coherence tomography and surgical outcomes in patients with submacular hemorrhage (SMH) secondary to age-related macular degeneration. METHODS: Medical charts of nine eyes of nine patients who underwent tissue plasminogen activator-assisted vitrectomy for SMH secondary to age-related macular degeneration were retrospectively reviewed. The preoperative height and lateral width of both SMH and pigment epithelial detachment documented with optical coherence tomography, were measured. The status of ellipsoid layers was also analyzed. RESULTS: Complete displacement of SMH from the fovea was achieved in all nine eyes. The preoperative status of the ellipsoid layer under the fovea was detectable in four eyes and absent in the remaining five eyes. Postoperative best-corrected visual acuity was significantly better in eyes with preoperative detectable ellipsoid layers (P < 0.01). Eyes with preoperative SMH heights <400 µm also exhibited better best-corrected visual acuity (P < 0.05). There was no significant correlation between postoperative best-corrected visual acuity and the specific features of pigment epithelial detachment, including height, lateral width, and number. CONCLUSION: The preoperative presence of detectable ellipsoid layers and a lower height of SMH may predict good visual prognosis. In contrast, no specific features of pigment epithelial detachment correlated with postoperative best-corrected visual acuity.

Idiopathic macular hole.

Idiopathic macular hole is a disease that arises from adhesion in the vitreomacular interface and can theoretically be treated by vitrectomy surgery. Surgical techniques include removal of the vitreous with or without simultaneous peeling of the internal limiting membrane (ILM), fluid-air exchange, and gas tamponade. Since the advent of microincision vitrectomy surgery, macular hole surgery has been performed with minimal invasiveness, and significant visual improvement is a common outcome. This chapter describes the pathology of this disease, including presurgical evaluation using optical coherence tomography (OCT), and then shows the fundamental techniques required for the surgery. Also important is the understanding of the postsurgical 'healing' process of the disease, which may confirm the fact that the subjective improvement is closely related to the retinal imaging obtained by OCT. More recent advances are the inverted ILM peeling technique for larger macular holes and 27-gauge vitrectomy that can potentially minimize the surgical invasiveness mainly by smaller wound construction and the reduced volume of irrigation during surgery.

Intravitreal bevacizumab alone or combined with macular laser photocoagulation for recurrent or persistent macular edema secondary to branch retinal vein occlusion.

Background. To evaluate the efficacy of intravitreal bevacizumab (IVB) injection with or without macular laser photocoagulation (MLP) for recurrent or persistent macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods. Thirty-four eyes underwent IVB injection for ME secondary to BRVO as a primary treatment. Twenty of the 34 eyes experienced recurrent or persistent ME after the first IVB. Nine of the 20 eyes (Group 1) were retreated with IVB combined with MLP. The remaining 11 eyes (Group 2) were retreated with IVB alone. Results. In Group 1, the postoperative best corrected visual acuity (BCVA) improved compared with the preoperative value at all follow-up visits, although no statistically significant improvement was observed at 6 months. In contrast, BCVA significantly improved from 0.53 to 0.40 at 6 months (P < 0.05) in Group 2. Conclusion. Combined therapy tended to have a smaller effect on visual acuity compared with IVB monotherapy.

Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal vasculopathy: 12-month LAPTOP study results.

PURPOSE: To compare the effect of photodynamic therapy (PDT) and intravitreal ranibizumab in patients with polypoidal choroidal vasculopathy (PCV). DESIGN: Randomized clinical trial. SETTING: Multicenter. STUDY POPULATION: Total of 93 patients with treatment-naïve PCV. INTERVENTION: Patients were randomized to 2 arms. Patients in the PDT arm underwent a single session of PDT with verteporfin, and patients in the ranibizumab arm received 3 monthly ranibizumab injections at baseline. Additional treatment was performed as needed in each arm. MAIN OUTCOME MEASURES: Primary outcome measurement was the proportion of patients gaining or losing more than 0.2 logarithm of minimal angle of resolution (logMAR) units from baseline. Mean change of logMAR and central retinal thickness (CRT) were also evaluated. RESULTS: In the PDT arm (n = 47), 17.0% achieved visual acuity gain, 55.3% had no change, and 27.7% experienced visual acuity loss. The results were 30.4%, 60.9%, and 8.7%, respectively, in the ranibizumab arm (n = 46), significantly better than the PDT arm (P = .039). In the PDT arm, mean CRT improved (366.8 ± 113.6 µm to 289.1 ± 202.3 µm, P < .001), but logMAR was unchanged (0.57 ± 0.31 to 0.62 ± 0.40). The ranibizumab arm demonstrated improvement in both CRT (418.9 ± 168.6 µm to 311.2 ± 146.9 µm, P < .001) and logMAR (0.48 ± 0.27 to 0.39 ± 0.26, P = .003). Mean change of logMAR was also greater in the ranibizumab arm (P = .011). CONCLUSION: Intravitreal injection of ranibizumab is more effective than PDT for treatment-naïve PCV.

Endoscope-assisted vitrectomy for retinal detachment in an eye with microcornea.

BACKGROUND: We report a case of an endoscope-assisted vitrectomy for the treatment of retinal detachment associated with microcornea in a normal size globe. SUBJECTS: A 26-year-old Japanese man was referred after complaining of visual acuity loss OD. Both eyes became aphakic because of surgery for congenital cataracts in infancy. The visual acuity was 0.02 OD. The corneal diameter was 7.5 × 7.0 mm and axial length was 23.89 mm. Retinal detachment was suspected, although the details were obscure because of nystagmus and small pupils. Endoscope-assisted, 23-gauge pars plana vitrectomy and encircling buckling were performed, and reattachment of the retina was achieved. OBSERVATIONS: Retinal breaks were identified, and peripheral parts of the retina were observed by endoscopy. CONCLUSIONS: Endoscope-assisted vitrectomy may be advantageous for the management of detachment in an eye with microcornea.

Effect of photodynamic therapy (PDT), posterior subtenon injection of triamcinolone acetonide with PDT, and intravitreal injection of ranibizumab with PDT for retinal angiomatous proliferation.

BACKGROUND: The purpose of this work was to compare the efficacy of photodynamic therapy (PDT) with or without posterior subtenon injections of triamcinolone acetonide (STA) or intravitreal injections of ranibizumab (IVR) for retinal angiomatous proliferation (RAP). METHODS: Thirty-seven eyes from 33 consecutive patients with RAP were treated by PDT monotherapy (Group 1), PDT combined with STA (Group 2), or PDT combined with IVR (Group 3). The best-corrected visual acuity, greatest linear dimension, central retinal thickness, and number of treatments were compared among the three groups. RESULTS: The change in mean best-corrected visual acuity (logMAR) at month 3, 6, and 12 after the initial treatment was better in Group 2 (-0.13, -0.23, and -0.21, respectively) and Group 3 (-0.018, 0.0028, and -0.0067, respectively) than in Group 1 (0.13, 0.19, and 0.23, respectively); Group 1 versus Group 2 was statistically significant (P = 0.018). The mean central retinal thickness was reduced from baseline in all groups, but the reduction amplitude was significantly greater in Group 2 than in Group 1 and Group 3. The mean number of treatments was significantly lower in Group 2 (1.1 ± 0.4) and Group 3 (1.5 ± 0.5) than in Group 1 (2.9 ± 0.9) in the 12 months after the initial treatment. CONCLUSION: Treatment with STA + PDT may be an effective therapy for RAP lesions over 12 months of follow-up.

Massive vitreous gel incarceration into the subretinal space following traumatic retinal detachment in a young patient: a case report.

PURPOSE: This paper reports a young patient with a traumatic rhegmatogenous retinal detachment and massive vitreous gel incarceration into the subretinal space, who was successfully treated with 23-gauge transconjunctival vitrectomy. CASE REPORT: An 11-year-old boy was referred to the authors' clinic with traumatic retinal detachment in the right eye, 2 weeks after ocular contusion in a baseball accident. At the time of the injury, emergency fundus examination by his local doctor had revealed vitreous hemorrhage in the inferior quadrant of the right eye. Visual acuity was 1.5. He had continued to play baseball as usual for 2 weeks after the injury. At his first visit to the authors' clinic, fundus examination showed a highly bullous retinal detachment involving the inferior two quadrants, associated with multiple irregular retinal breaks. There was an oval hole in the inferior quadrant which was 10-disc diameter × 5-disc diameter in size and was surrounded by edematous and hemorrhagic retina. The macula remained attached. Absolute rest for 4 hours in the supine position with binocular occlusion did not diminish the height of the retinal detachment. A 23-gauge three-port pars plana vitrectomy combined with 360° circumferential buckling was performed under general anesthesia. The lens was retained. Incarceration of massive vitreous gel, including vitreous hemorrhage into the subretinal space through the largest break, was observed during vitrectomy. Reattachment of the retina was achieved by fluid-air exchange and internal tamponade using SF(6) gas. At follow-up at 9 months, the retina remained attached and visual acuity in the right eye was 1.2.

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema.

PURPOSE: To evaluate the geographic pattern of central retinal sensitivity and its resolution shortly after intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME). METHODS: Twenty eyes of 20 patients who underwent IVTA for the treatment of DME were reviewed retrospectively. Early changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), photoreceptor inner and outer segments (IS/OS) line and central retinal sensitivity were analyzed. Retinal sensitivity was measured at 40 points within the central 10 degrees of the macula with the Micro Perimeter 1 before treatment, and at 1 week and 1 month after IVTA. RESULTS: Mean BCVA and CMT improved significantly at 1 week and 1 month after IVTA. Mean retinal sensitivity, however, showed no significant improvement at 1 week (P = 0.238), but did show significant improvement at 1 month (P = 0.0003). Mean retinal sensitivity of the points at the central 2 degrees, which was significantly lower than that at 6 and 10 degrees before treatment, showed improvement similar to those of 6 and 10 degrees after IVTA. Mean retinal sensitivity in the nasal quadrant of the macular area had the best sensitivity at all time points, and improved more than it did in the other quadrants. Mean retinal sensitivity in the central 2 degrees was better in the eyes with complete IS/OS line (P < 0.0001). CONCLUSIONS: BCVA and CMT improved significantly after IVTA for DME. Retinal sensitivity also showed significant, albeit relatively slow, improvement. The nasal quadrant of the macular area showed more improvement than did any other quadrant.

23-gauge vitrectomy assisted by combined endoscopy and a wide-angle viewing system for retinal detachment with severe penetrating corneal injury: a case report.

BACKGROUND: We report a case of traumatic retinal detachment in an eye with severe corneal opacity that was successfully treated using 23 gauge (G) transconjunctival vitrectomy assisted by endoscope and a wide-angle viewing system. CASE PRESENTATION: A 22-year-old Japanese man was referred to our hospital with the suspicion of traumatic retinal detachment of the right eye, 1 month after an open globe eye injury due to fireworks. At the time of his first visit, his best-corrected visual acuity was hand motion in the right eye. A 23 G three port pars plana vitrectomy was conducted in combination with ophthalmic endoscope and a wide-angle viewing system. Endoscopy revealed a retinal detachment in the inferior quadrant with tiny retinal breaks. Primary reattachment of the retina was achieved by tamponade of SF6 gas. Five months after the vitrectomy, penetrating keratoplasty was performed and visual acuity recovered to 0.02. Optical coherent tomography revealed thinning of the retina, which might be the cause of the remaining poor vision. CONCLUSION: 23 G vitrectomy assisted by combined endoscopy and a wide-angle viewing system could be advantageous in managing visualization constraints due to penetrating trauma.

Serous retinal detachment associated with retinal vein occlusion.

PURPOSE: To study the pathomorphology of serous retinal detachment (RD) associated with retinal vein occlusion by optical coherence tomography (OCT). DESIGN: Retrospective chart review. METHODS: Ninety-one eyes of 91 patients with macular edema associated with retinal vein occlusion had undergone a comprehensive ophthalmologic examination, including measurement by spectral-domain OCT. RESULTS: Eyes with macular edema associated with retinal vein occlusion typically showed foveal cystoid spaces and marked retinal swelling, especially in the outer retina. In addition, 76 eyes (83.5%) showed serous RD involving the fovea, which ranged in thickness from 64 microm to 871 microm (219.2 +/- 161.6 microm). Fifty-two eyes showed a small pointed RD, with a small base. The point of the RD was always located beneath the fovea, where the outer surface of the swollen neurosensory retina seemed to be contracted inward, resulting in development of the pointed RD. Two eyes with no RD at the initial visit developed such a pointed RD during follow-up. In contrast, 24 eyes showed a more dome-shaped RD, with a large base, and in 18 eyes, a pointed RD seen at the initial visit changed into a dome-shaped RD during follow-up. In some cases, small outer retinal discontinuity was seen on the external surface of the swollen neurosensory retina. CONCLUSIONS: In eyes with retinal vein occlusion, a small pointed RD initially developed just beneath the fovea, but subsequently changed into a dome-shaped RD. Based on the findings by OCT, we hypothesize that the foveal architecture, especially that of the Müller cell cone, is involved in the formation of serous RD.

Retinal structural changes associated with retinal arterial macroaneurysm examined with optical coherence tomography.

PURPOSE: To study the retinal structural changes associated with a retinal arterial macroaneurysm and their association with visual prognosis. METHODS: We studied retrospectively the medical records of 44 eyes of 44 patients with a retinal arterial macroaneurysm; all eyes showed hemorrhagic and/or exudative changes of the fovea with a visual disturbance. The retinal structural changes were examined by optical coherence tomography (OCT). RESULTS: At the initial visit, 30 eyes (68%) showed severe hemorrhagic complications. In eyes with subretinal hemorrhage beneath the fovea, retinal structure was relatively preserved at the initial visit. At the final visit, however, foveal structure was often degenerated, especially in its outer aspect, with limited visual recovery. The 14 eyes (32%) with minimal hemorrhagic complications showed an extensive exudative change caused by the aneurysm. In 13 of these eyes, OCT examination revealed extensive retinal edema, predominantly in the outer retina. Retinal edema beneath the fovea caused a focal serous retinal detachment in 12 eyes. Eight eyes with extensive exudative change showed an accumulation of hard exudates in the macular area, and visual recovery of these eyes was often limited. CONCLUSION: Subretinal hemorrhage or extensive exudative change from a retinal arterial macroaneurysm can cause destruction of the foveal outer photoreceptor layer, resulting in a poor visual outcome.

Lamellar macular hole formation in patients with diabetic cystoid macular edema.

PURPOSE: To report lamellar macular hole formation in four patients with diabetic cystoid macular edema (CME). METHODS: A review of the medical records of four patients with diabetic CME in whom lamellar macular hole formation was observed. The morphologic changes of CME, seen using optical coherence tomography (OCT), and best-corrected visual acuity were evaluated. RESULTS: Lamellar macular hole formation had occurred, as determined by slit-lamp biomicroscopy and OCT. Although the inner retinal layer had disappeared, the outer retinal layer was preserved. On OCT, the reflective line of an epiretinal membrane or a posterior hyaloid membrane was seen on the surface of juxtafoveal retina, and visual acuity remained unchanged in all four patients. CONCLUSION: In diabetic patients with CME, the CME occasionally changes spontaneously to a lamellar macular hole. Although the central cystoid space disappears and foveal thickness decreases after this transformation, visual acuity may be little affected as long as the structure of the outer retina remains intact.

Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy.

UNLABELLED: We retrospectively investigated the relationship between the appearance of IS/OS line on OCT images and visual acuity after resolution of DME by vitrectomy. Postoperative visual acuity of eyes with complete IS/OS after resolution of DME was significantly better than that without complete IS/OS, though macular edema was completely resolved in both groups. PURPOSE: To evaluate the correlation between photoreceptor layer status following resolution of diabetic macular edema (DME) by pars plana vitrectomy (PPV) and final visual acuity (VA). METHODS: We retrospectively studied a series of 69 eyes from 58 patients with DME who were treated with PPV. Of the 69 eyes, 37 that were examined by optical coherence tomography (OCT) for at least 6 months and that showed a final macular thickness of less than 250 microm were included in this study. We assessed the integrity of the photoreceptor inner and outer segments (IS/OS) line in the fovea, using OCT in relation to their VA and other characteristics. RESULTS: There were no differences in initial VA or in foveal thickness between eyes with or without complete IS/OS at final observation. However, final VA without complete IS/OS was significantly poorer (P = 0.004). VA had improved by more than 2 lines in eight of ten eyes with complete IS/OS and in ten of 27 eyes without complete IS/OS; the groups differed significantly with regard to this percentage (P = 0.03). CONCLUSIONS: The postoperative photoreceptor status of the fovea is closely related to the final VA after resolution of DME by PPV.