Usha Chakravarthy

Treatment of age-related subfoveal neovascular membranes by teletherapy : a pilot study

This investigation was designed to determine whether low dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularisation. Nineteen patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 10 or 15 Gy of 6 MV photons and seven patients who declined treatment were followed up as controls. Six controls and all treated patients had completed follow up times of at least 12 months. Visual acuity was maintained or improved in 78% and 63% of treated patients at their 6 and 12 month follow up examinations respectively. By contrast visual acuity showed steady deterioration in six of seven controls. Significant neovascular membrane regression, as measured by image analysis, was recorded in 68% and 77% of treated patients at 6 and 12 months post-radiation, whereas the membranes in all seven control patients showed progressive enlargement. This study suggests that low doses of radiation can maintain central vision and induce regression of subfoveal neovascular membranes of ARMD in a significant proportion of patients. We now believe it appropriate to proceed to a prospective randomised study to test this hypothesis further.

Stereotactic radiotherapy for neovascular age-related macular degeneration: 52-week safety and efficacy results of the INTREPID study.

PURPOSE To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (nvAMD). DESIGN Randomized, double-masked, sham-controlled, multicenter, clinical trial. PARTICIPANTS Two hundred thirty patients with onset of nvAMD within 3 years who received 3 or more injections of ranibizumab or bevacizumab within the preceding year and who needed continuing ranibizumab or bevacizumab treatment. INTERVENTIONS Participants were randomized 2:1:2:1 to 16 Gy plus pro re nata (PRN) ranibizumab, sham 16 Gy plus PRN ranibizumab, 24 Gy plus PRN ranibizumab, or sham 24 Gy plus PRN ranibizumab, respectively. MAIN OUTCOME MEASURES The primary efficacy end point was the mean number of ranibizumab injections at 52 weeks. Secondary end points were change in mean best-corrected visual acuity (VA), loss of fewer than 15 Early Treatment Diabetic Retinopathy Study letters, gain of 0 or more and 15 or more letters, and change in angiographic total lesion size and choroidal neovascularization (CNV) lesion size. RESULTS Both the 16-Gy and 24-Gy SRT arms received significantly fewer ranibizumab treatments compared with the sham arms: mean number of treatments, 2.64 (median, 2), 2.43 (median, 2), and 3.74 (median, 3.5), respectively (P = 0.013 and P = 0.004, respectively, vs. sham). Change in mean VA was -0.28, +0.40, and -1.57 letters for the 16-Gy, 24-Gy, and sham arms, respectively. The 16-Gy, 24-Gy, and sham arms lost fewer than 15 letters in 93%, 89%, and 91% of eyes, respectively, with 53%, 57%, and 56% gaining 0 or more letters, respectively, and 4% gaining 15 letters or more in all arms. Mean total angiographic lesion area changed by -1.15 mm(2), +0.49 mm(2), and +0.75 mm(2), respectively; mean CNV lesion area decreased by 0.16 mm(2), 0.18 mm(2), and 0.10 mm(2), respectively. Optical coherence tomography central subfield thickness decreased by 85.90 μm, 70.39 μm, and 33.51 μm, respectively. The number of adverse events (AEs) and number of serious AEs (SAEs) were similar across arms. No AEs were attributed to radiation. No SAEs occurred in the study eye. CONCLUSIONS A single dose of SRT significantly reduces ranibizumab retreatment for patients with nvAMD, with a favorable safety profile at 1 year. Whereas chronic nvAMD typically results in loss of VA over time, SRT is associated with relatively well-preserved VA over 1 year. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Radiation therapy for age-related macular degeneration.

Neovascular age-related macular degeneration is the most common cause of severe irreversible blindness in the Western world in people older than age 50. Laser photocoagulation is the only proven treatment for this disease; however, fewer than 20% of patients are eligible for this treatment because the majority of choroidal neovascularization membranes are not visible by ophthalmoscopy or angiography. In addition, many patients elect not to undergo this treatment because laser treatment of subfoveal neovascular membranes results in immediate and permanent central visual loss. Several treatments are under investigation, including external-beam radiation therapy. There are multiple publications of early trials using radiation therapy, but to date there is only one randomized published study. This article reviews these trials and summarizes the status of radiation therapy as a treatment for macular degeneration.

Stereotactic radiotherapy for neovascular age-related macular degeneration: year 2 results of the INTREPID study.

PURPOSE To determine the safety and efficacy of low-voltage, external-beam, stereotactic radiotherapy (SRT) for patients with neovascular age-related macular degeneration (AMD). DESIGN Randomized, double-masked, sham-controlled, multicenter, clinical trial. PARTICIPANTS A total of 230 participants with neovascular AMD who received ≥ 3 ranibizumab or bevacizumab injections within the preceding year and requiring treatment at enrollment. METHODS Participants received 16 Gray, 24 Gray, or sham SRT. All arms received pro re nata (PRN) ranibizumab for 12 months, with PRN bevacizumab or ranibizumab thereafter. MAIN OUTCOME MEASURES Mean number of PRN injections; best-corrected visual acuity (BCVA); loss of <15 Early Treatment of Diabetic Retinopathy Study letters; change in optical coherence tomography central subfield thickness; and change in angiographic total lesion area and choroidal neovascularization (CNV) area. RESULTS At year 2, the 16 and 24 Gray arms received fewer PRN treatments compared with sham (mean 4.5, P = 0.008; mean 5.4, P = 0.09; and mean 6.6, respectively). Change in mean BCVA was -10.0, -7.5, and -6.7 letters for the 16 Gray, 24 Gray, and sham arms, respectively, with 46 (68%), 51 (75%), and 58 participants (79%), respectively, losing <15 letters. Mean central subfield thickness decreased by 67.0 μm, 55.4 μm, and 33.3 μm, respectively. Mean total active lesion area increased by 1.0, 4.2, and 2.7 mm(2), respectively. Mean CNV area decreased by 0.1 mm(2) in all groups. An independent reading center detected microvascular abnormalities in 6 control eyes and 29 SRT eyes, of which 18 were attributed to radiation; however, only 2 of these possibly affected vision. An exploratory subgroup analysis found that lesions with a greatest linear dimension ≤ 4 mm (the size of the treatment zone) and a macular volume greater than the median (7.4 mm(3)) were more responsive to SRT, with 3.9 PRN injections versus 7.1 in comparable sham-treated participants (P = 0.001) and mean BCVA 4.4 letters superior to sham (P = 0.24). CONCLUSIONS A single dose of SRT significantly reduces intravitreal injections over 2 years. Radiation can induce microvascular change, but in only 1% of eyes does this possibly affect vision. The best response occurs when AMD lesions fit within the treatment zone and they are actively leaking.

UK AMD EMR USERS GROUP REPORT V: benefits of initiating ranibizumab therapy for neovascular AMD in eyes with vision better than 6/12.

Background/aims To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy. Methods Multicentre national nAMD database study on patients treated 3–5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections. Results The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12–6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001–0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12. Conclusions All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients’ funding.

Radiotherapy for choroidal neovascularisation of age-related macular degeneration: a fresh perspective.

Radiotherapy for choroidal neovascularisation of age-related macular degeneration: A fresh perspective

Changes in Neovascular Lesion Hyperreflectivity After Anti-VEGF Treatment in Age-Related Macular Degeneration: An Integrated Multimodal Imaging Analysis.

PURPOSE To correlate presence of hyperreflective material (HRM) on spectral-domain optical coherence tomography (SD-OCT) with color fundus photography (CFP) in patients with different subtypes of neovascular age-related macular degeneration (n-AMD). METHODS Retrospective assessments were made at baseline and months 1, 3, and 12 after initiation of treatment. At baseline, CFP images were graded for the presence of blood, fibrin and lipid exudates, and retinal angiograms for n-AMD subtype. At the four selected visits, SD-OCT scans were graded for HRM type (well-defined or undefined) and location (subretinal, intraretinal, and subretinal pigment epithelium [RPE]), integrity of RPE, ellipsoid zone, and external limiting membrane (ELM). RESULTS A total of 121 eyes with active n-AMD from 117 patients were included. At baseline, undefined HRM was strongly associated with fibrin on CFP (χ2 = 39.87; P < 0.001). The overall prevalence of HRM decreased from 85.9% at baseline to 52.9% by month 12. From baseline to month 12, undefined HRM decreased (53.7% vs. 7.4%, respectively) and well-defined HRM increased (32.2% vs. 45.5%, respectively). Sub-RPE HRM, which was infrequent at baseline, increased up to 30.6% by month 12. At month 12, eyes with no HRM had the best mean final best-corrected visual acuity (BCVA), and those with undefined HRM the worst. Multivariate regression analysis showed that ELM disruption at both baseline and month 12 was a negative predictive factor for final BCVA (P = 0.001 and P < 0.001, respectively), whereas presence of subretinal fluid at month 12 and number of treatments were positive predictors for final BCVA (P = 0.007 and P = 0.041, respectively), but the covariates describing HRM did not reach statistical significance in these models. CONCLUSIONS In eyes with n-AMD, location and morphology of HRM changed after anti-VEGF treatment, and differences were observed in the various choroidal neovascularization (CNV) subtypes. After anti-VEGF treatment, it was well-defined HRM in the sub-RPE space that was observed mostly.

Multimodal imaging of posterior ocular involvement in McArdle's disease: Multimodal imaging in McArdle's disease

Giuseppe Casalino* MD FEBO Wing Chan MD FRCOphth Clara McAvoy MD FRCOphth Michele Coppola MD Francesco Bandello MD FEBO Alan C Bird MD FRCOphth Usha Chakravarthy MD PhD *Royal Eye Unit, Kingston Hospital NHS Foundation Trust, London, UK Moorfields Eye Hospital NHS Foundation Trust, London, UK Ophthalmology Macular Service, Belfast Health and Social Care Trust, Belfast, UK Ophthalmology Unit, Ospedale di Desio, ASST Monza, Monza, Italy Department of Ophthalmology, Scientific Institute San Raffaele, Vita-Salute University, Milan, Italy E-mail: peppecasalino@gmail.com Submitted: 12 June 2017 Revised: 13 September 2017 Accepted for publication: 30 September 2017