Khurram M. Chaudhary

An Evidence-Based Meta-analysis of Vascular Endothelial Growth Factor Inhibition in Pediatric Retinal Diseases: Part 1. Retinopathy of Prematurity

Recently there has been interest in the novel, off-label use of anti-vascular endothelial growth factor (anti-VEGF) agents for various stages of retinopathy of prematurity (ROP). The authors report on the quality and depth of new evidence published from 2009 to 2011 concerning the treatment of retinopathy of prematurity (ROP) with bevacizumab (Avastin; Genentech Inc., South San Francisco, CA) as either primary or adjunctive treatment for ROP. There is significant variability in the evidence, quality, and design of the studies available in the literature. There has been a trend in the scientific literature of the past 2 years toward larger, multi-center, randomized studies investigating the role of bevacizumab in the treatment of ROP. More recent evidence suggests that monotherapy with intravitreal bevacizumab may be a viable first-line treatment for select cases of zone I ROP and possibly for posterior zone II disease. Adjunctive treatment with bevacizumab may enhance outcomes in patients treated with laser photocoagulation or pars plana vitrectomy. However, there are significant concerns regarding its long-term safety profile. Further prospective studies are warranted to more fully determine the role of anti-VEGF therapy in this disease.

Early initial clinical experience with intravitreal aflibercept for wet age-related macular degeneration

Background Age-related macular degeneration (AMD) is a degenerative process that leads to severe vision loss. Wet AMD is defined by choroidal neovascularisation, leading to the accumulation of subretinal fluid (SRF), macular oedema (ME), and pigment epithelium detachments (PED). Purpose To evaluate the initial clinical experience of conversion from bevacizumab or ranibizumab to aflibercept in wet AMD patients. Methods Records of 250 consecutive wet AMD patients were retrospectively reviewed. Of 250 patients, 29 were naive (with no previous treatment), and 221 were previously treated with bevacizumab (1/3) or ranibizumab (2/3). On average, converted patients received 14 injections every 6 weeks on a treat-and-extend regimen with Avastin or Lucentis before being converted to aflibercept every 7 weeks on average (no loading dose) for three doses. For the purposes of this study, we concentrated on the patients converted to aflibercept since the number of naive patients was too small to draw any conclusion from. Snellen (as logMar) visual acuities, and optical coherence tomography (OCT) were compared predrug and postdrug conversion. Results Converted patients did not show a significant difference in visual acuity or average OCT thickness from preconversion values; however, small improvements in ME (p=0.0001), SRF (p=0.0001), and PED (p=0.008) grading were noted on average after conversion to aflibercept. Conclusions No significant difference in visual outcome or average OCT thickness was observed when switched from bevacizumab or ranibizumab q6 week to aflibercept 7-week dosing, on average. Mild anatomic improvements did occur in converted patients with regard to ME, SRF and PED improvement, on average, after conversion to aflibercept, and aflibercept was injected less frequently. No serious adverse reactions, including ocular infections or inflammation, as well as ocular and systemic effects were noted.

Pars plana vitrectomy in the management of patients diagnosed with endophthalmitis following intravitreal anti-vascular endothelial growth factor injection.

Purpose: To evaluate the possible benefit of pars plana vitrectomy in the treatment of patients with endophthalmitis following antivascular endothelial growth factor (VEGF) injection. Method: The authors retrospectively reviewed the medical records of all patients in their practice with a diagnosis of endophthalmitis from January 1, 2007, through December 31, 2011. Only those with a clinical presentation consistent with endophthalmitis after intravitreal anti-VEGF injection were included. Clinical data that were collected and recorded included visual acuities and the method of initial and subsequent treatment of endophthalmitis following anti-VEGF injection: tap and injection of intravitreal antibiotics (TAP) and tap and inject with subsequent pars plana vitrectomy (VIT). Results: The authors identified 23 patients meeting criteria. Nineteen patients had received bevacizumab and four patients had received ranibizumab. The median time from last injection to presentation was 4 days (range, 1–18 days) with a median follow-up of 15 months (range, 5–48 months) after being diagnosed of endophthalmitis. Nine patients had positive cultures. The median baseline visual acuity (preendophthalmitis) was 20/70 (range, 20/25 to counting fingers at 2 ft) with a median presenting visual acuity of counting fingers at 1 ft (range, 20/50 to light perception vision). Overall, 90% (9/10) of the patients in TAP only group regained visual acuity within 1 line or better of baseline versus 46% (6 of 13) in the TAP and VIT group. Only one of the patients treated with TAP alone suffered more than one line of visual acuity loss. Conclusion: Patients diagnosed with endophthalmitis after anti-VEGF intravitreal injection who underwent TAP regained baseline visual acuity more often than those who underwent TAP and VIT. This study did not support a benefit for VIT in all patients, rather only in those cases who warranted it because of worsening clinical course. The study suggests that TAP is a viable primary intervention for endophthalmitis after anti-VEGF injection.

Optical coherence tomography-based positioning regimen for macular hole surgery.

Purpose: To evaluate an optical coherence tomography (OCT)–based positioning regimen for patients undergoing macular hole surgery. Method: We reviewed the medical records of all patients in our practice who underwent macular hole repair, instituting a modified OCT-based positioning regimen from November 1, 2011 through July 31, 2013. The regimen consisted of prone positioning at the conclusion of surgery with daily OCT imaging until the hole was confirmed closed at which point positioning was halted. Clinical data that were collected and recorded included visual acuities, stage of hole, size of hole, chronicity, preoperative and postoperative OCT imaging, and length of follow-up. Results: We identified 33 patients (35 eyes) with a mean baseline visual acuity of 20/220, a mean hole size of 465 &mgr;m. The mean final (postoperative) visual acuity was 20/135 with a mean follow-up of 7.7 months. Six patients (17%) in our study were diagnosed with myopic degeneration. Thirteen patients (37%) were found to have chronic (≥12 months) holes, and 19 (54%) were found to have large holes (>400 &mgr;m). Overall, 28 eyes (80%) had persistent closure of macular holes with an OCT-based positioning regimen. In the absence of high risk factors, such as myopic degeneration, chronic or large holes, the closure rate was 92%. In the presence of 2 or 3 of these risk factors, the closure rate was 85% and 74%, respectively. Conclusion: The presence of 2 or 3 high risk factors, such as myopic degeneration, chronic holes (≥12 months), or large holes (>400 &mgr;m) can compromise outcomes resulting in reopening after apparent early closure. Based on the presence of these risk factors, a modified postoperative positioning regimen can be used to obtain complete and persistent closure.

Macular epiretinal membrane peeling treatment outcomes in young children.

Purpose: The purpose of this study was to describe macular epiretinal membrane (ERM) peeling treatment outcomes in young children. Methods: The medical records of all vitrectomies from 1998 through 2010 were retrospectively reviewed. Patients who were selected were 16 years or younger and had primarily macular or posterior pole disease secondary to an ERM. Patients with retinopathy of prematurity, Coats disease, Norrie disease, and incontinentia pigmenti were excluded. Fourteen patients underwent vitrectomy with ERM peeling, and their preoperative and postoperative visual acuities were compared. Results: The mean age at surgery was 8 years, with an average follow-up of 4.2 years (range, 6 months to 11 years). The average presenting visual acuity was 20/258. Average postoperative visual acuity was 20/100, with improvement in 12 patients (86%) and no change of visual acuity in 2 patients (14%). Conclusion: Pediatric ERMs respond well to vitrectomy and membrane peel with a low likelihood of recurrence. Other associated pathology, such as familial exudative retinopathy and combined hamartomas of the retina and retinal pigment epithelium, was associated with complications, such as delayed-onset rhegmatogenous retinal detachment from peripheral traction and recurrence of ERM in 7% of patients.

PROPORTION OF PATIENTS WITH MACULAR HOLE SURGERY WHO WOULD HAVE BEEN FAVORABLE OCRIPLASMIN CANDIDATES: A Retrospective Analysis.

Purpose: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients. Methods: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined “favorable” ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ⩽400 &mgr;m. The authors further categorized “optimal” candidates as age ⩽65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ⩽400 &mgr;m. Results: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ⩽400 &mgr;m in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates. Conclusion: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.

Immune Reconstitution Uveitis Complicated by Vitreoretinal Traction and Formation of a Retinal Tear

The authors report a case of immune reconstitution uveitis induced by cytomegalovirus retinitis with subsequent development of vitreoretinal traction and a resultant retinal tear.