LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

Comparison of subretinal aflibercept vs ranibizumab vs bevacizumab in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA in naïve submacular haemorrhage secondary to nAMD. "The Submarine Study".

OBJECTIVE: To compare efficacy and safety profile of subretinal aflibercept, ranibizumab, and bevacizumab in the context of pars plana vitrectomy, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage (SMH) due to naïve neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective interventional cohort study. PARTICIPANTS: 123 eyes of 123 patients treated with subretinal aflibercept (n = 41, 33%), ranibizumab (n = 41,33%), and bevacizumab (n = 41, 33%). METHODS: Review of electronic medical records for best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) at baseline and 24 months after treatment. MAIN OUTCOME MEASURES: BCVA, CST, and number of intravitreal anti VEGF over 24 months. RESULTS: Mean age of patients was 80.5 ± 5.5 years, 43.9% were female. Mean time from symptom onset until surgery was 1.1 days (range 0-3 days). In all cases, the SMH did not reach the arcades. CST at baseline was 627 ± 140 µ, 739 ± 54 µ, and 793 ± 93 µ (p = 0.0001) for aflibercept, ranibizumab, or bevacizumab, respectively. Baseline BCVA (logMAR) was 0.65 ± 0.13, 0.69 ± 0.96, and 0.74 ± 0.81 (p = 0.0041) for aflibercept, ranibizumab, and bevacizumab, respectively. All three groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no statistically significant difference at the final BCVA (p = 0.789). The mean number of anti VEGF given during follow-up period was 5.2 ± 0.81, 4.4 ± 0.63, and 5.5 ± 0.95 (p = 0.0001) for aflibercept, ranibizumab, and bevacizumab, respectively. CONCLUSION: This study shows that aflibercept, ranibizumab, and bevacizumab in a subretinal manner in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage secondary to naïve nAMD work with the same efficacy and safety profile.

RHEGMATOGENOUS RETINAL DETACHMENT AFTER INJECTION OF TISSUE PLASMINOGEN ACTIVATOR AND GAS FOR SUBMACULAR HEMORRHAGE SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The purpose of this study was to describe the rate, clinical characteristics, and outcomes of rhegmatogenous retinal detachment (RRD) after injection of tissue plasminogen activator (TPA) and gas for submacular hemorrhage displacement. METHODS: Retrospective analysis of consecutive cases developing RRD after TPA injection and gas for submacular hemorrhage displacement. The rate of RRD was calculated, and a description of RRD clinical characteristics was performed. Anatomic and visual outcomes after RRD repair were analyzed. RESULTS: Ninety eyes of 90 patients were analyzed. Tissue plasminogen activator was given intravitreally in 53 eyes (59%) and subretinally in 37 eyes (41%). RRD occurred in 6 of 90 eyes (7%). Of these, one had intravitreal TPA and five had vitrectomy with subretinal TPA ( P = 0.04). The mean age was 75 (64-93) years. The median time of RRD occurrence was 42 (1-134) days. All cases had macular involvement. Two cases had PVR at presentation. Vitrectomy was performed in all cases and silicone oil used in five, all of which resulted in permanent silicone oil retention. One case (17%) achieved primary single surgery success. The median final visual acuity was 1.8 logMAR (20/1,260 Snellen). CONCLUSION: The RRD rate after submacular hemorrhage displacement was 7% in our case series. Rhegmatogenous retinal detachment occurred more commonly after vitrectomy with subretinal TPA injection. The visual and anatomic outcomes were poor, with a high rate of retained silicone oil and recurrent RRD.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.

PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm. DESIGN: Randomized, open-label, multicenter superiority study. PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (≤ 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium. METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 µg], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 µg] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45° for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up. MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up. RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference ß, 1.9 [-11.0; 14.9]; P = 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group. CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Bilateral Central Retinal Vein Occlusion in a Neonate.

AIM: To report the management of a neonate who presented with simultaneous bilateral central retinal vein occlusion (CRVO) secondary to septicemia. DESIGN: Case Report. RESULTS: A full-term infant was treated for neonatal sepsis with thrombocytopenia. He presented with poorly dilating pupil, disc edema, dilated retinal veins, perivascular exudation, retinal hemorrhages in all four quadrants radiating from the optic nerve to the ora serrata (no Roth spots), with cystoid macular edema (CME) in both the eyes. His TORCH serology was negative and peripheral blood film was normal. He was diagnosed as presumptive bilateral inflammatory CRVO with CME secondary to septicemia. He received bilateral intravitreal bevacizumab injections. After the injection, his pupils dilated completely while retinal hemorrhages and CME reduced. CONCLUSION: CRVO may present as a rare complication in neonates suffering from septicemia. Apart from the systemic treatment, aggressive ocular treatment is needed to salvage the eyes with severe ischemia.

Massive retinal infiltrates as the presenting sign of chronic myeloid leukemia: Clinical and imaging features of leukemic retinopathy.

PURPOSE: To describe the clinical and optical coherence tomography (OCT) features of two cases with bilateral diffuse retinal infiltrates as the only presenting feature of chronic myeloid leukemia (CML) on initial diagnosis and upon relapse. METHODS: We reported two patients with CML, one at initial diagnosis and one in remission who presented with bilateral subacute visual impairment. Fundal examination revealed bilateral symmetrical leukostatic appearance with increased vascular tortuosity, diffuse retinal infiltrates with size up to 6 disk diameters, retinal hemorrhages, and Roth's spots. OCT showed multiple intra-retinal hyper-reflective foci corresponding to intra-retinal hemorrhages, and outer retinal hyper-reflective foci in area corresponding to retinal infiltrate. The different retinal layers were relatively preserved and distinguishable. RESULTS: White cell count (WCC) were elevated in both patients ranging from 544 to 810 × 109/L. Bone marrow biopsy confirmed the diagnosis of CML in the patient without prior diagnosis and relapse of CML in another patient. Cytogenetic test detected Abelson murine leukemia (ABL) - breakpoint cluster region (BCR) fusion transcript in both cases. Both patients were started on oral imatinib, subsequently WCC returned to within normal values in both cases. Vision and OCT abnormalities improved and reduction in retinal hemorrhages and infiltrates were observed in follow up. CONCLUSION: This report highlights the important role of ophthalmologists and detailed fundus examination in making a prompt diagnosis of leukemia in patients with visual complaints. Appropriate systemic investigation and hematologist referrals for prompt treatment of CML may improve survival rate and preserve vision.

Multimodal evaluation of hemorrhages within intraretinal cystoid spaces in a blood-fluid level presentation.

INTRODUCTION: We describe characteristic findings on multimodal evaluation and the features of hemorrhage within a foveal cystoid space in a patient presenting cystoid macular edema secondary to Branch Retinal Vein Occlusion (BRVO). CASE DESCRIPTION: We report a case of a 64-year-old diabetic male patient presenting gradual blurry vision in the left eye. Fundoscopic findings were suggestive of BRVO, such as hard exudates and mild venous engorgement superotemporally and diffuse macular intraretinal hemorrhages. In the foveal area, there was cystoid edema with blood-fluid level (BFL) inside one of the cystoid spaces. Retina multimodal evaluation, including color, blue filter, and red-free fundus photography, fluorescein angiography, fundus autofluorescence, and spectral-domain optical coherence tomography (SD-OCT) B and C scan imaging, confirmed blood within foveal cystoid space. The patient underwent antiangiogenic therapy with significant improvement of macular edema and reduction of the cystoid space after 3 months. In addition, there was a resolution of visual symptoms. The cystoid space previously partially filled with blood, persisted, despite presenting smaller volume and medium reflectivity in the SD-OCT. CONCLUSIONS: Multimodal evaluation of blood-fluid level within foveal cystoid space in patients with BRVO has not been described previously. Identification of this sign may support the diagnosis of retinal vein occlusion in doubtful cases and further studies must be carried out to establish if the presence of BFL correlates with visual outcomes.

Subretinal Injection Under Perfluorocarbon Liquids to Avoid Foveal Dehiscence.

SUMMARY: We describe a novel technique modification of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular haemorrhage, using a perfluorocarbon liquid filled vitreous cavity and an eccentric injection point, with a viscous fluid injector system controlled injection. PURPOSE: To describe a novel method of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular hemorrhage. METHOD: Description of technique with illustrative case description and details of four cases treated. The subretinal injection is delivered under a perfluorocarbon liquid bubble filling 80% of the vitreous cavity. An eccentric injection point is used and the tissue plasminogen activator injected under a pneumatically controlled viscous fluid injection system with a 38-g polyimide cannula and low injection pressure. RESULTS: Four cases have been treated with controlled subretinal injection extending under the fovea without dehiscence, including one case with apparent preexisting foveal dehiscence and a preretinal clot. CONCLUSION: The technique allows the creation of a low more diffuse subretinal bleb compared with without perfluorocarbon liquid, minimizing hydraulic stress on the fovea during injection and could be applied to other subretinal injection scenarios where the fovea is at risk of hydraulic blowout. Further experience of the technique is needed to validate this initial report.

INFUSION-ASSISTED EVACUATION OF SUBMACULAR HEMORRHAGE.

PURPOSE: To report a novel surgical technique for evacuating submacular hemorrhage using the infusion stream of a 25-gauge vitrectomy system. METHODS: Surgical case and video. RESULTS: A 54-year-old man was taken to the operating room for a total hyphema, nonclearing vitreous hemorrhage, and elevated intraocular pressure after multiple tractional retinal detachment repairs by an outside surgeon. Intraoperatively, the hyphema and vitreous hemorrhage were cleared, and the source of bleeding was discovered to be an avulsed vessel through a pre-existing retinal break just superior to the optic nerve. A large submacular hemorrhage was also present that was unable to be drained through the break by aspiration alone. With the vitreous cavity under fluid, the infusion cannula was manipulated to guide the infusion stream onto the macula. The stream was directed in a distal to proximal manner toward the retinal break, and the submacular blood was successfully expressed out through the break. Postoperatively, the retina remained attached with almost complete resolution of the submacular hemorrhage. CONCLUSION: Using the mechanical pressure of the infusion stream can be an effective method for evacuating large subretinal hemorrhages.

Naïve subretinal haemorrhage due to neovascular age-related macular degeneration. pneumatic displacement, subretinal air, and tissue plasminogen activator: subretinal vs intravitreal aflibercept-the native study.

OBJECTIVE: We aimed to compare visual and anatomical outcome in subretinal aflibercept vs. intravitreal aflibercept in the context of Pars Plana Vitrectomy (PPV), pneumatic displacement with subretinal air and subretinal tPA in patients with naïve submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective interventional cohort study. PARTICIPANTS: 80 patients treated with subretinal aflibercept vs. intravitreal aflibercept in the context of PPV, subretinal air and subretinal tPA in patients with SMH secondary to naïve nAMD. METHODS: Records were reviewed. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 24 months after treatment. MAIN OUTCOME MEASURES: BCVA, CST, and number of anti VEGF treatment over follow-up period. RESULTS: The average duration from onset of symptoms to surgery was 1.26 days (range 0-3 days). Based on review of OCT images, SMH was subretinal in all 80 patients (100%), and sub-RPE in 29 patients (36.3%). Forty-one patients (51.25%) were treated with subretinal aflibercept ("subretinal group"), and 39 patients (48.75%) were treated with intravitreal aflibercept injections ("intravitreal group"). The groups were well balanced for age and gender p = 0.6588, and p = 0.263, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). The mean number of anti VEGF given during follow-up period was statistically significantly lower in the "subretinal group" (p < 0.0001). CONCLUSION: This study shows better management of the CNV, with a statistically significant lower need for anti-VEGF injections when treated with subretinal aflibercept compared to intravitreal application.

Early anti-VEGF treatment for radiation maculopathy and optic neuropathy: lessons learned.

Radiation therapy has saved both sight and life for eye cancer patients. The most common methods include ophthalmic plaque brachytherapy and external beam techniques. However, subsequent dose-dependent radiation vasculopathy invariably occurs within and around the targeted zone. In 2006, Finger discovered that periodic intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab could reverse and suppress intraocular radiation vasculopathy. At first, it was administered at the onset of radiation-related vision loss. Though bevacizumab induced regression of macular oedema, retinal haemorrhages and cotton-wool infarcts, most patients were left with residual retinal damage, manifest as metamorphopsia and loss of vision. These results led to earlier and earlier anti-VEGF interventions: first after signs of progressive radiation retinopathy, and then for signs of radiation maculopathy, and finally for high-risk eyes with no clinical signs of retinopathy. Earlier initiation of intravitreal anti-VEGF therapy typically resulted in greater restoration and preservation of macular anatomy, reductions of retinal haemorrhages, resolution of cotton-wool spots and vision preservation. Recent research on optical coherence tomography angiography (OCT-A) has revealed that radiation vasculopathy occurs prior to clinical ophthalmic signs or symptoms. Therefore, it seemed reasonable to consider treating high-risk patients (considered certain to eventually develop radiation maculopathy) to prevent or delay vision loss. Herein, we describe the evolution of treatment for radiation maculopathy as well as recent research supporting anti-VEGF treatment of high-risk patients immediately following radiation to maximize vision outcomes.

Antiplatelet and anticoagulant therapy in patients with submacular hemorrhage caused by neovascular age-related macular degeneration.

PURPOSE: Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication. METHODS: We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake. RESULTS: A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm2. Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm2 vs. 21.91 mm2) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants. CONCLUSION: Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated.

Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

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.

Vitrectomy with subretinal tissue plasminogen activator (r-TPA) and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for submacular hemorrhages treatment: Retrospective analysis of 22 cases.

BACKGROUND: Macular hemorrhages are a severe complication of other retinal pathologies, such as age-related macular degeneration (AMD) or macroaneurysms. Their therapeutic approach is not standardized, and can vary from observation to surgical treatment. MATERIAL AND METHODS: Retrospective analysis of 22 cases of macular hemorrhage, treated with vitrectomy associated to subretinal rTPA and intravitreal anti-VEGF over a period of 5 years. RESULTS: 22 eyes of 22 patients were included, of which 12 (52%) were women. The mean age at diagnosis was 84.4 years. 13 patients were pseudophakic (54.1%) and 19 (86.36%) had previous ophthalmological comorbidities. The etiology of the macular hemorrhage was AMD in 19 patients (86.36%). The mean of best VA corrected at diagnosis was 24.55 (Early Treatment Diabetic Retinopathy Study score -ETDRS), with a statistically significant improvement to 36.78 3 months after surgery (p = 0.011). With an average of 23.5 months of follow-up, no differences in prognosis associated with the etiology or size of the hemorrhage were observed. CONCLUSION: The treatment of macular hemorrhages by vitrectomy, subretinal rTPA and antiVEGF improves the visual prognosis of affected patients.

Incidence, risk factors and outcomes of submacular haemorrhage with loss of vision in neovascular age-related macular degeneration in daily clinical practice: data from the FRB! registry.

PURPOSE: The main purpose of the study was to report the estimated incidence, cumulative rate, risk factors and outcomes of submacular haemorrhage (SMH) with loss of vision in neovascular age-related macular degeneration (nAMD) receiving intravitreal injections (IVT) of vascular endothelial growth factor (VEGF) inhibitor in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes receiving IVTs of VEGF inhibitors (ranibizumab, aflibercept or bevacizumab) for nAMD from 1 January 2010 to 31 December 2020 that were tracked the Fight Retinal Blindness! registry. Estimated incidence, cumulative rate and hazard ratios (HR) of SMH with loss of vision during treatment were measured using the Poisson regression, Kaplan-Meier survival curves and Cox proportional hazard models. RESULTS: We identified 7642 eyes (6425 patients) with a total of 135 095 IVT over a 10-year period. One hundred five eyes developed SMH with loss of vision with a rate of 1 per 1283 injections (0.08% 95% confidence interval [95% CI] [0.06; 0.09]). The estimated incidence [95% CI] was 4.6 [3.8; 5.7] SMH with loss of vision per year per 1000 treated patients during the study. The cumulative [95% CI] rate of SMH per patient did not increase significantly with each successive injection (p = 0.947). SMH cases had a mean VA drop of around 6 lines at diagnosis, which then improved moderately to a 4-line loss at 1 year. CONCLUSIONS: Submacular haemorrhage (SMH) with loss of vision is an uncommon complication that can occur at any time in eyes treated for nAMD in routine clinical practice, with only limited recovery of vision 1 year later.

CONTRAST-TO-NOISE RATIO IS A USEFUL PREDICTOR OF EARLY DISPLACEMENT OF LARGE SUBMACULAR HEMORRHAGE BY INTRAVITREAL SF6 GAS INJECTION.

PURPOSE: To investigate predictors of early displacement of submacular hemorrhage (SMH) by simple intravitreal SF6 gas injection. METHODS: This retrospective study included 16 eyes of 16 consecutive patients (age: 74.5 ± 7.7 years; 15 men) with large SMH treated with simple intravitreal SF6 gas before inception of subretinal tissue plasminogen activator injection at our institution. The SMH displacement was graded at 1-week posttreatment as 0, 1, or 2. Central retinal thickness, central choroidal thickness, SMH height, SMH area, disease duration, use of anticoagulant or antiplatelet drugs, and contrast-to-noise ratio (CNR) of SMH on optical coherence tomography images were recorded. Correlations between displacement grading and baseline parameter were analyzed. RESULTS: Univariable correlation analysis revealed association of the 1-week displacement grading with the CNR (P = 0.004; r = -0.68) and SMH height (P = 0.03; r = -0.55). The CNR was most strongly associated with 1-week displacement on multivariable correlation analysis (P = 0.01; ß = -0.60). CONCLUSION: Findings of the present study showed that the CNR of SMH was a useful predictor of early displacement of large SMH after simple intravitreal SF6 gas injection. When vitrectomy with subretinal injection of tissue plasminogen activator is difficult in patients with large SMH, with low CNR on optical coherence tomography, simple intravitreal SF6 gas injection may be a treatment option.

Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial.

BACKGROUND: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options. METHODS: TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 µg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms. DISCUSSION: The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10.

Not-so-minimal for minimally invasive surgery.

Sub-macular hemorrhage poses a potential threat to vision if left untreated. The preferred surgical technique to clear sub-macular hemorrhage includes vitrectomy followed by retinotomy using a 41G needle with subsequent injection of recombinant tissue plasminogen activator (r-tPA) followed by air/SF6 injection into the sub-retinal space. A malleable nature, increased resistance, and the cost of the 41G needle limit its use. We evaluated the safety and efficacy of a 26G needle for retinotomy as a supplement for the 41G needle in a series of six subjects with sub-macular hemorrhage. A slight modification in the procedure was done by injecting air into the sub-retinal space prior to the r-tPA injection. We found that our technique of using the 26G needle for retinotomy is safe and effective due to its stable nature and self-sealing properties. An air injection prior to r-tPA allows for increased bioavailability of the drug by preventing efflux due to its tamponading effect.