Exudative Macular Degeneration Research Articles

Changes in Macular Pigment Optical Density after Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration: A Pilot Study.

Background: This study aimed to evaluate the effects of faricimab intravitreal injections in patients with exudative age macular degeneration (nAMD) after the loading dose using spectral domain optical coherence tomography (SD-OCT) and macular pigment optical density (MPOD). Methods: In this observational prospective study, we enlisted a total of 12 consecutive eyes of 12 patients (six females, six males; mean age 70.47 ± 2.46 years) affected by nAMD who consecutively presented to the Eye Clinic of the University of Naples "Federico II" and Monaldi Hospital of Naples, from June 2023 to December 2023. All patients received four once-monthly intravitreal injections of faricimab (6 mg/0.05 mL) (loading phase). At baseline and 1 month after the fourth faricimab monthly injection, all patients underwent assessment of best correct visual acuity (BCVA) and ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure (IOP), fundus biomicroscopy, SD-OCT, and MPOD. Results: A total of 12 eyes of 12 patients (six women, six men; mean age 70.47 ± 2.46 years) were included in this study. A statistically significant raise in BCVA and MOPD parameters was shown between baseline and after the loading phase (p < 0.001). Conclusions: Intravitreal injections of faricimab led in the short term to a significant functional and MPOD improvement along with a decrease in central macular thickness (CMT) and thus appears to be an effective treatment option without relevant adverse effects. MOPD may be considered as a prognostic factor associated with a good visual prognosis after intravitreal injections treatment.

Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.

To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD). Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols. We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias = - 0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making. Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.

Pre- and perioperative prophylaxis of anti-VEGF therapy in patients with exudative macular degeneration

Macular degeneration is one of the leading causes of blindness worldwide. Nowadays, the gold standard treatment for its exudative form is intravitreal injections with vascular growth factor inhibitor preparations performed on a once-daily basis. Great importance is now attached to the appropriate prophylaxis in the pre- and perioperative period in order to minimise the risk of complications, which often lead to irreversible damage to vision.

Impact du confinement français en 2020 sur la prise en charge des patients atteints de dégénérescence maculaire liée à l’âge exsudative

To assess the impact of the measures taken during the lockdown period from March 17to May 11, 2020on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours. In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded. In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss. Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections.

Botulinum toxin type A in multimodal management of age-related macular degeneration and related diseases

Age related macular degeneration (AMD) is the major cause of visual loss in the aging population in the Western world. In past decade, intra ocular injections of anti-vascular endothelial growth factor (anti-VEGF) pharmaceuticals have revolutionized therapy for exudative (edematous-wet) AMD and become standard practice for the near term. However repeated intra-ocular injections are required for years and long terms results have been limited. The pathogenesis of this condition is multifactorial involving genetic, ischemic, inflammatory factors leading to neovascularization, edema and retinal pigment epithelial scaring resulting in photoreceptor destruction. Based on coincidental observation in reduction in AMD related macular edema on ocular coherence tomography (OCT) in a BoNT A treated patient with facial movement disease, BoNT-A at conventional doses targeting the para orbital area was added to therapeutic regiment in a small number of patients with exudative macular degeneration or related diseases. Measurements of edema and choriocapillaris using Spectral Doman (OCT) and Ocular Coherence Angiography (OCT-A) and Snellen visual acuity were made over the evaluation period. 15 eyes in 14 patients averaged 361 μm central sub foveal edema (CSFT) pre injection and average of 266 μm (CSFT) post injection over an average of 21 months and 5.7 cycles using BoNT A alone at conventional doses (n = 86 post injection measurements, paired t-test p < 0.001 two tailed). Visions at baseline in patients with 20/40 or worse averaged 20/100- pre injection improved to an average of 20/40- in the post injection period (n = 49 measurements p < 0.002 paired t-test). The previous data was added to a group of 12 more severely afflicted patients receiving anti VEGF (aflibercept or bevacizumab) (total 27 patients). With this 27-patient group, patients were followed for an average of 20 months and receiving average of 6 cycles at conventional doses. Improvement in exudative edema and vision were noted with pre injection baseline CSFT average 399.5, post injection average 267, n = 303 post measurement, independent t-test P < 0.0001.). Snellen vision 20/128 baseline average improved to average of 20/60- during post injection period (n = 157 post injection measurements, p < 0.0001 paired t-test to baseline). No substantial adverse effects were noted. Cyclic effects were noted corresponding to duration of action of BoNT-A on a number of patients. The above data is preliminary and is skewed toward early leakage for all conditions.BoNT A may have a role in the treatment of aged related macular degeneration.Controlled studies are needed with careful staging and baseline stratifications for multi-modal management paradigms. The findings are discussed relative to known botulinum toxin type A pharmacology and AMD pathogenesis.

Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects.

Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro models compared to real clinical cases. Among the several potential mechanisms examined, particular attention was paid to histologic alterations and molecular cascades. Physical or biochemical resistance to vascular invasion from the choroid offered by Bruch's membrane, the role of fibroblast growth factor 2 and vascular endothelial growth factor, resident or recruited stem-like/progenitor cells, and other angiogenic promoters were taken into account. Even if the exact mechanisms are still partially obscure, experimental models are progressively enhancing our understanding of neovascularization etiology. Choroidal neovascularization (CNV) over melanoma, osteoma, and other tumors is not rare and is not contraindicative of malignancy as previously believed. In addition, CNV may represent a late complication of either benign or malignant choroidal tumors, stressing the importance of a long follow-up.

Polypoidal Choroidal Vasculopathy: An Update on Diagnosis and Treatment

Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid that leads to hemorrhagic and exudative macular degeneration. It may cause significant vision loss and thus affect the quality-of-life and psychological well-being. Non-invasive, non-ICGA-based OCT criteria have shown reliable results to plan adjunct photodynamic therapy (PDT) treatment, with the complete and consistent coverage of polypoidal lesions (PL) and branching neovascular network (BNN). The safety and efficacy of anti-vascular endothelial growth factor (anti-VEGF) monotherapy and its combination with verteporfin PDT have been established. However, treatment is still challenging due to frequent follow-ups, non-availability of PDT, and need for multiple anti-VEGF injection visits that increase the treatment burden and lead to patients being lost to follow-up. Effective treatments that prolong intervals between injections while maintaining vision and anatomical gains remain a critical unmet need. Longer acting molecules, like brolucizumab, have shown non-inferiority in BCVA gains and superior anatomical outcomes compared to other anti-VEGF agents. Newer therapies in the pipeline to enhance the efficacy and longevity of treatment include Faricimab and a port delivery system (PDS). This review summarizes the most recent diagnostic and treatment approaches in PCV to offer better treatment avenues.

Correlation between choroidal vascularity index, flow pattern and neovascular activity in treatment naive eyes of age related macular degeneration

: To study the correlation between choroidal vascularity index, flow pattern and neovascular activity in treatment naive eyes of age related macular degeneration.: Cross-sectional analysis of 46 treatment naive eyes diagnosed with exudative age related macular degeneration. All patients underwent spectral domain optical coherence tomography, fluorescein angiography, indocyanine green angiography and OCTA. The Choroidal Vascularity Index (CVI) and OCTA vascular features at initial and last visit were analyzed after anti vascular endothelial growth factor (VEGF) treatment. These changes were correlated with the disease activity on SD-OCT and OCTA.: Mean age was 66.34 ± 7.2 years. Mean sub foveal choroidal thickness was 215.39±102.378 µm at baseline and 198.42±101.049 µm at 3 months (p=0.07). The mean CVI was 63.73±5.28% at baseline &amp; 64.59±4.87% at 3 months (p=0.754). Pattern of network on OCTA was sea-fan in 20(43.5%), medusa head in 8(17.4%), indistinct in 18(39.1%) at baseline and sea-fan in 6(13%), medusa head in 6(13%), indistinct in 28(60.9%) and mixed in 6(13%) at 3 months. The signs of activity on OCT changes after 3 months (p =0.001).On OCTA 36 eyes had active network at baseline &amp; 34 eyes had inactive network at the last follow up (p=0.001).: Choroidal vascularity Index showed no correlation with various patterns of CNV and showed no significant change with anti VEGF treatment. Post treatment network patterns showed no significant correlation with the OCT activity even though the OCTA showed an active network.

Monitor mean changes in intraocular pressure following intravitreal injection of bevacizumab in exudative age related macular degeneration and proliferative diabetic retinopathy

Objective: To monitor the effect of Intravitreal injection of bevacizumab on intraocular pressure in order to know whether intraocular pressure lowering medication or paracentesis is required prophylactically or thereafter.&#x0D; Subjects and methods: A prospective intervensional case series of 90 eyes with proliferative diabetic retinopathy and exudative Age related macular degeneration was done who received intravitreal injection of bevacizumab. Intraocular pressure was recorded with Goldman applantaion tonometer at baseline, and then after procedure at 5min, 30 min, 01 hours and 01 weeks. The pateints data was recorded of age, gender, disease, intraocular pressure, history of glaucoma, previous surgery, phakic status and topical and systemic medications.&#x0D; Results: The mean baseline intraocular pressure was found to be 13.54±2.1 in Proliferative diabetic retinopathy and 12.76±1.8 in Exudative Age related macular degeneration (p-value 0.046). The mean intraocular pressure elevation following Intravitreal bevacizumab at 5min was 32.89±6.3 in proliferative diabetic retinopathy and in exudative Age related macular degeneration was 32.18±5.7 (p-value 0.510), at 30 min was 16.71±2.6 and 15.53±2.4 (p-value &lt;0.024), at one hour was 14.20±2.0 and 13.47±1.9 (p-value 0.095) and at one week 13.82±1.7 and 13.06±1.7 (p-value 0.126) in proliferative diabetic retinopathy and exudative Age related macular degeneration respectively. So there was no significant difference between the two diseases.&#x0D; Conclusion: There is abrupt and transient rise in the intraocular pressure following intravitreal injection of bevacizumab, but it did not remain elevated for longer duration hence there was no need of intraocular pressure lowering medication and paracentesis.

Dual Sensory Impairment: The Correlation between Age Related Macular Degeneration and Sensorineural Hearing Loss.

The pathogeneses of age-related macular degeneration (AMD) and age-related hearing impairment are not yet fully understood. If AMD and age-related hearing impairment are correlated, the cause of both may be a result of a common vulnerability. The aim of this study was to assess the interrelation between age-related macular degeneration and age-related hearing loss. Material and methods: In our case-control analysis, the hearing conditions of 40 subjects with AMD were compared with 40 age-matched healthy controls. In all patients, retinal changes were certified by clinical examinations, optical coherence tomography (OCT), and fluorescein angiography (FA). All subjects were inspected with pure tone audiometry (PTA), impedance audiometry, and speech audiometry. Results: A significant correlation (p < 0.001) was identified between age-related macular degeneration and age-related hearing impairment. The predominant hearing impairment in this case was sensorineural (SNHL). Of the patients diagnosed with AMD, SNHL was found in 88.89% of those with exudative macular degeneration and in 67.74% of those with atrophic macular degeneration. In contrast, we found that a significant proportion of the control group had normal hearing. Conclusion: One possible explanation for the association between retinal and cochlear impairment may be due to a melanin disorder.

Histology of neovascular myopic macular degeneration

To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24–89 years; axial length: 25.5 ± 3.1 mm; range: 20–37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0–31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch’s membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.

CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

Switching Between Aflibercept and Ranibizumab in the Treatment of Refractory Exudative Age-related Macular Degeneration

Introduction: Aflibercept and ranibizumab have become the most used drugs in the treatment of wet age-related macular degeneration. Some patients; however, do not respond to aflibercept and ranibizumab treatment. Our aim was to determine whether the switch from aflibercept to ranibizumab, and then switchback, is effective in a group of patients poorly responding to aflibercept. We assessed best corrected visual acuity, central retinal thickness, and the presence of intra- and subretinal fluid (respectively).&#x0D; Material and methods: We conducted a retrospective comparative case series study. Twenty eyes of 20 patients, who had no inhibition of disease activity after at least one year of treatment with aflibercept, were included in the study. If after switch to ranibizumab the response to the drug was again inadequate, we returned to aflibercept. We divided the study population into two groups: treatment- naïve and patients who had received injections before entering the Drug Program for the Treatment of Age-Related Exudative Macular Degeneration.&#x0D; Results: We observed an improvement in both best corrected visual acuity and central retinal thickness parameters, but only in the treatment-naïve group. We did not observe any statistically credible effects for sub- and intraretinal fluid in the studied groups.&#x0D; Conclusions: Drug conversion may be beneficial for patients poorly responding to primary therapy. Greater improvement is seen in previously untreated patients.

Therapy of Age-related Exudative Macular Degeneration with Anti-vascular Endothelial Growth Factor Drugs: An Italian Real Life Study

Aim: To evaluate the real utilization of ranibizumab and aflibercept in the daily management of patients with neovascular age-related macular degeneration (nAMD) treated at the Eye Clinic of Campania University L.Vanvitelli. Background: Therapy with anti-vascular endothelial growth factor represents the gold standard in wet age-related macular degeneration. There are nonreal life italian studies of this therapy in the literature. Objective: To analyze in our sample the post-therapy variations of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) observed at the end of a 12-month follow-up period. Methods: This real-life study analyzes 109 patients that underwent monthly checks for the first 4 months and then every 2 months until the end of the 12-month follow-up. The sample was first analyzed in its entirety, subsequently subdivided into 3 groups based on baseline BCVA, age, and the number of intravitreal injections performed, in order to identify possible predictive elements of the anti-VEGF response. Results: On average, patients underwent 4.16 ± 1.58 intravitreal anti-VEGF injections in 1 year. At the end of the 12-month follow-up, the patients’ average BCVA increased from 33.01 letters to 33.75 letters (+0.74 ± 9,4 letters), while the average CRT decreased from 346.86 µm to 265.39 µm (-81.47 ± 121 µm). Conclusion: The study shows the efficacy of anti-VEGF therapy in the stabilization of BCVA in nAMD, confirming the differences in visual outcomes compared to clinical trials, mainly for economic-organizational reasons.

Effects of cigarette smoking on sensorineural hearing impairment and age related macular degeneration.

INTRODUCTIONCigarette smoking has been causally associated with various diseases, and among the numerous harmful effects of smoking is included its impact on the senses of vision and hearing. The purpose of this study is to evaluate the impact of cigarette smoking on the visual and auditory functions.METHODSIn this analytic study, hearing and smoking status of 40 patients with agerelated macular degeneration (AMD) were analyzed with 40 age-matched control subjects without AMD. In all subjects (n=80), retinal status was investigated by optical coherence tomography (OCT), with analyses of thickness central subfield (TCS) and thickness average cube (TAC) of the macula. All participants were examined with pure tone audiometry. Audiometric trials comprised pure tone bone and air conduction. The smoking history of all the subjects was recorded in detail.RESULTSA significant correlation was found between smoking status and visual (p<0.001) and hearing impairment (p<0.05). Cigarette smoking was found to be highly correlated with sensorineural hearing impairment and exudative macular degeneration.CONCLUSIONSCigarette smoking damage anti-oxidative systems and tissue metabolism. We have underlined a clear correlation between the risk of sensorineural hearing impairment, exudative macular degeneration and cigarette smoking. Our findings may result in future screening of smokers to identify any hearing and vision impairment and for improving smoking cessation interventions.

The use of multimodal imaging in the evaluation of a patient with central retinal artery occlusion in the setting of asteroid hyalosis: a case report

BackgroundA central retinal artery occlusion (CRAO) is an ophthalmic emergency due to its strong association with cerebrovascular and cardiovascular morbidity and mortality. A timely diagnosis is necessary but difficult in the setting of dense asteroid hyalosis, as typical fundoscopic findings can be obscured. We present a case where multimodal imaging in an eye with an obscured fundus could lead to timely diagnosis and management of CRAO in a patient with acute vision loss.Case presentationA 94-year-old Caucasian woman with a history of exudative macular degeneration presented to the retina clinic with acute vision loss in one eye over the course of an afternoon. The patient had dense asteroid hyalosis, and a direct retinal exam was not possible. Multimodal imaging suggested a CRAO diagnosis. The patient received digital ocular massage directly prior to undergoing fluorescein angiography (FANG), which confirmed the diagnosis. The patient was transported from clinic to the emergency room for an emergency stroke workup, which revealed a spontaneous echo in the left atrial appendage, and the patient was started on antiplatelet therapy. When she presented for follow-up within a week, the patient noted that her vision had improved at the time of digital ocular massage and continued to improve thereafter. Her FANG showed marked reperfusion of the retina, and she subsequently has completely regained her baseline visual acuity.ConclusionsMultimodal imaging is useful in evaluating visual loss in patients with acute vision loss. In addition, ocular massage is a simple, low-risk intervention that may have benefit in the treatment of acute CRAO. Patients who present to ophthalmologists with an acute CRAO need an emergency referral for evaluation of cerebrovascular and cardiovascular comorbidities.

OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

Treatment for a Subtype of Exudative Macular Degeneration—Another Mountain Climbed

Treatment for a Subtype of Exudative Macular Degeneration—Another Mountain Climbed

Aucuba japonica extract inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy, with its bioactive components preventing VEGF-induced retinal vascular hyperpermeability.

Neovascularization in the retina is common pathophysiology of diabetic retinal microvasculopathy and exudative macular degeneration. Our study assessed the inhibitory activity of an ethanol‐based extract of Aucuba japonica (AJE) on abnormal angiogenesis in the retina with a hyperoxia‐induced neovascular retinopathy model. The inhibitory effects of aucubin, quercetin, and kaempferol, bioactive compounds, from A. japonica, on retinal vascular hyperpermeability were also examined. On the 7th postnatal day (P7), the C57BL/6 pups were exposed to a hyperoxic environment with 75% oxygen to develop the experimental angiogenesis in retinas. On the 12th postnatal day (P12), the pups were then returned to the normal atmospheric pressure of oxygen. From P12 to P16, the administration was intraperitoneal. The dose per day was 250 mg per kg weight. Retinal neovascularization was measured with retinal flat mounts prepared on P17. We also measured the vascular leakage mediated by the vascular endothelial growth factor (VEGF) in retinas. Mice treated with AJE had markedly smaller neovascular lesions, in comparison with vehicle‐administered mice. AJE downregulated the expression of both VEGF protein and mRNA. In addition, aucubin, quercetin, and kaempferol ameliorated VEGF‐induced retinal vascular leakage. The results of our study suggest that AJE is a potent antiangiogenic substance. AJE could also serve as a therapeutic agent for abnormal growth of vessels in the retina in patients with ischemic retinopathy. The bioactive compounds of AJE may be responsible for its antiangiogenic abilities.

Randomized Safety and Feasibility Trial of Ultra-Rapid Cooling Anesthesia for Intravitreal Injections

To test the safety and preliminary efficacy of rapid, nonpharmacologic anesthesia via cooling for intravitreal injections. Single-center, randomized phase 1 dose-ranging safety study (ClinicalTrials.gov identifier, NCT02872012). Adults 18 years of age or older with a diagnosis of exudative macular degeneration or diabetic macular edema requiring bilateral anti-vascular endothelial growth factor therapy were included. A handheld device was developed to provide anesthesia via cooling to a focal area on the surface of the eye before intravitreal treatment (IVT). In 22 patients undergoing bilateral IVT, 1 eye was randomized to receive standard of care (SOC) lidocaine-based anesthesia and the other eye received cooling-anesthesia at 1 of 5 different temperatures and cooling times. Subjective pain was assessed via the visual analog scale (VAS; range, 1-10) at 2 time points: (1) immediately after IVT and (2) 4 hours after IVT. Treated eyes were assessed for ocular safety 24 hours after IVT. We determined the occurrence of adverse events in eyes treated with cooling anesthesia. Mean VAS pain scores immediately after IVT and 4 hours after IVT in eyes receiving cooling anesthesia were compared with eyes receiving SOC. A total of 44 eyes were treated, 22 with cooling anesthesia and 22 with SOC. No dose-related toxicity was found with cooling anesthesia. Mild, transient adverse events were recorded in 32% of patients treated with cooling anesthesia versus 44% of patients receiving SOC. The mean±standard error of the mean (SEM) VAS pain scores immediately after intravitreal injection were 2.3 ± 0.4 for patients receiving SOC and 2.2 ± 0.6 in patients receiving -10° C cooling anesthesia (P= 0.8). Mean±SEM pain scores 4 hours after injection were 1.6 ± 0.4 for SOC and 1.2 ± 0.5 in the combined -10° C arms (P= 0.56). Total mean±SEM procedure time was 124 ± 5 seconds for patients treated with cooling anesthesia versus 395 ± 40 seconds for SOC (P < 0.0001). Ultra-rapid cooling of the eye for anesthesia was well tolerated, with -10° C treatment resulting in comparable levels of anesthesia to SOC with a reduction in procedure time.