THE LATEST PUBLISHED RESEARCH

Treatment of Neovascular AMD with Intravitreal Bevacizumab
Researchers from Beirut, Lebanon, conducted this prospective, open-label, nonrandomized clinical study to demonstrate the efficacy of intravitreal bevacizumab for treatment of neovascular age-related macular degeneration (AMD). Included in the study, which was conducted at the American University of Beirut and Hotel Dieu de France Retina Clinics, were 51 patients (51 eyes) with subfoveal choroidal neovascularization (CNV) resulting from AMD.

All patients had already completed 12 months of follow up and the criteria for reinjection were: presence of fluid in the macula, increased central retinal thickness (CRT) of at least 100 µm, loss of at least 5 letters of vision associated with increased fluid in the macula, new classic CNV or new macular hemorrhage. The researchers used the proportion of eyes losing <15 letters of vision after 12 months as the main outcome measure.

All 51 patients completed the additional 12 months and, according to the researchers, mean visual acuity improved from 45.7 letters at baseline to 54.3 letters at 24 months (p=.001). Forty-seven eyes (92.2%) lost fewer than 15 letters. The researchers observed that mean CRT decreased from 327.4 µm at baseline to 246.6 µm at 24 months (p<.001) and while a mean of 1.5 injections were administered over the course of the second year, they noted no serious ocular or systemic side effects.

Eyes with neovascular AMD treated with intravitreal bevacizumab over 2 years had significant anatomic and functional improvement compared with baseline, the study researchers found. They suggest the need for further studies to confirm the long-term efficacy and safety of this treatment.

Source: Bashshur ZF, Haddad ZA, Schakal AR, et al. Intravitreal bevacizumab for treatment of neovascular age-related macular degeneration : the second year of a prospective study. Am J Ophthalmol 2009;48(1):59-65.

Efficacy of Variable Dosing Regimen with Intravitreal Ranibizumab for Neovascular AMD
In this open-label, prospective, single-center, uncontrolled clinical study, investigators enrolled AMD patients with neovascularization involving the central fovea and a central retinal thickness (CRT) of at least 300 µm as measured by OCT to receive 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Their intention was to assess the long-term efficacy of a variable-dosing regimen with ranibizumab in the Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular Age-Related Macular Degeneration (AMD) Treated with intraOcular Ranibizumab (PrONTO) Study. The investigators followed patients for 2 years.

During the first year, retreatment with ranibizumab was performed at each monthly visit if any criterion was fulfilled such as an increase in OCT-CRT of at least 100 µm or a loss of 5 letters or more. During the second year, the retreatment criteria were amended to include retreatment if any qualitative increase in the amount of fluid was detected using OCT.

A total of 40 patients were enrolled and 37 completed the 2-year study. The investigators reported that at month 24, the mean visual acuity (VA) improved by 11.1 letters (p<.001) and the OCT-CRT decreased by 212 µm (p<.001). VA improved by 15 letters or more in 43% of patients. These VA and OCT outcomes were achieved with an average of 9.9 injections over 24 months.

The investigators determined that the PrONTO Study using an OCT-guided variable-dosing regimen with intravitreal ranibizumab resulted in VA outcomes comparable with the outcomes from the phase III clinical studies, but fewer intravitreal injections were required.

Source: Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO study. Am J Ophthalmol 2009;48(1):43-58.

12-Month Results of Primary Treatment with Intravitreal Bevacizumab for Retinal Angiomatous Proliferation
In this Italian study, researchers evaluated the short-term efficacy and safety of intravitreal bevacizumab for the treatment of retinal angiomatous proliferation.

A total of 17 eyes from 16 patients with newly diagnosed retinal angiomatous proliferation underwent intravitreal injections of bevacizumab, 1.25 mg. The researchers scheduled patients for three monthly bevacizumab injections and examined Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity, central macular thickness on optical coherence tomography and fluoresce in findings before and after treatment. They followed the patients for 12 months.

The mean best-corrected visual acuity (± standard deviation [SD]) at baseline was 39.53 (±10.40) letters (Snellen equivalent: 20/42) and at 12 months after treatment, the mean best-corrected visual acuity (±SD) improved significantly (p=0.0000001) to 47.88 (±11.78) letters (Snellen equivalent: 20/28). The study researchers discovered that best-corrected visual acuity improved 3 ETDRS lines or more in 3 (17.65%) of 17 treated eyes, 14 (82.35%) eyes were stable and 15 (88.23%) eyes gained 1 or more ETDRS lines. Furthermore, the mean central macular thickness (±SD) at baseline was 297 (±60.72) µm and at 12 months after treatment, the mean central macular thickness (±SD) reduced significantly (p=0.000001) to 237 (±28.80) µm. At the 12-month follow up, absence of fluorescein leakage was demonstrated in 14 (82%) of 17 treated eyes. No ocular or systemic adverse effects from treatment were encountered.

The researchers in this study posited that the 12-month results of intravitreal bevacizumab for retinal angiomatous proliferation are promising with no apparent short-term safety concerns. They noted that treated eyes had a significant functional and anatomical improvement, though further studies are needed to determine long-term efficacy and safety.

Source: Gharbiya M, Allievi F, Recupero V, et al. Intravitreal bevacizumab as primary treatment for retinal angiomatous proliferation: twelve-month results. Retina 2009;29(6):740-749.

Comparison of Bevacizumab Treatments for Neovascular AMD
To determine whether reduced light dose photodynamic therapy (PDT) combined with bevacizumab will decrease the number of bevacizumab treatments required over 6 months compared to bevacizumab monotherapy in neovascular age-related macular degeneration (AMD), 36 patients with neovascular AMD were recruited for this randomized, double-masked, controlled Canadian clinical trial.

Patients received intravitreal bevacizumab plus PDT using a light dose of either 25 J/cm² (group 1) or 12 J/cm² (group 2) or intravitreal bevacizumab plus sham PDT (group 3) and returned monthly for possible retreatment with bevacizumab or combination therapy (with a 3-month minimum interval between combination treatments). Retreatment decisions were primarily based on optical coherence tomography. The main outcome measure was the mean number of bevacizumab treatments required over 6 months. It was noted that patients required a mean of 2.8 bevacizumab treatments in group 1 and 2.5 in group 2, compared to 5.1 in group 3 (p=0.005 and p<0.001, respectively).

Based on the study findings, combination bevacizumab and 25-J/cm² or 12-J/cm² PDT significantly reduced the number of bevacizumab treatments required over six months. This study was powered to examine number of treatments, but not visual acuities. Nevertheless, visual acuities responded favorably in all three groups. Further studies will be helpful to explore visual outcomes.

Source: Potter MJ, Claudio CC, Szabo SM. A randomized trial of bevacizumab and reduced light dose photodynamic therapy in age-related macular degeneration: the VIA study. Br J Ophthalmol 2009;June 10 [Epub ahead of print]. DOI :10.1136/bjo.2008.155531.

Changes in Focal Macular Electroretinograms Following PDT for AMD
To determine the changes in the focal macular electroretinograms (FMERGs) after PDT combined with triamcinolone acetonide for age-related macular degeneration, 34 eyes that were successfully treated by PDT with a posterior juxtascleral injection of triamcinolone acetonide were studied. FMERGs, optical coherence tomography and indocyanine green angiography were performed before and after the PDT.

It was found that the mean amplitudes of the FMERGs were not significantly decreased 1 week after PDT with triamcinolone acetonide (p>0.05) and the mean ratio of the FMERG b-wave 1 week after PDT to that before PDT was 1.09, with an indistinct hypofluorescence at the site of the PDT (18 eyes), and the ratio was 1.09 in the eyes with a distinct hypofluorescence border (16 eyes; p<0.05).

While the combined use of triamcinolone acetonide with PDT mitigated the depression of retinal function soon after PDT, there were cases of severe choroidal hypoperfusion corresponding to the site of the laser spot that impaired retinal function in comparison to cases with mild hypoperfusion. Even with severe choroidal hypoperfusion, the deterioration in retinal function was relatively mild, with the b-wave FMERG reduced by only 10%.

Source: Ishikawa K, Nishihara H, Ozawa S, et al. Focal macular electroretinograms after photodynamic therapy combined with posterior juxtascleral triamcinolone acetonide. Retina 2009;29(6):803-810.

Preventing Pain During Panretinal Photocoagulation with Oral vs. Topical Diclofenac
To investigate the effect of pretreatment oral and topical diclofenac on pain reduction during panretinal laser photocoagulation (PRP) for proliferative diabetic retinopathy (PDR), the authors of this prospective, randomized, double-masked, placebo-controlled clinical trial randomly assigned 90 patients with PDR requiring PRP for the first time to one of three study groups: oral diclofenac (n=30), topical diclofenac (n=31) or placebo (n=29).

They administered study medications before the first PRP treatment and recorded pain levels experienced during and 15 minutes after PRP on a visual analog scale (VAS). Also, they recorded pain levels during a second PRP session, performed on a later date with no pretreatment medications. The primary outcome measures were the mean VAS pain scores during the first PRP treatment, while secondary outcome measures were the mean VAS pain scores 15 minutes after the first PRP and during the second PRP, as well as reported side effects after the first PRP.

According to the authors, mean VAS pain scores during the first PRP were: oral diclofenac, 25.7±19.9; topical diclofenac, 33.8±27.9; and placebo, 41.3±31.0. The pain score difference between oral diclofenac and placebo was both clinically significant (≥13) and statistically significant (p=0.02), whereas differences between oral and topical diclofenac (p=0.20) and topical diclofenac and placebo (p=0.33) were not. In addition, multivariate regression analysis for age, gender and total laser energy demonstrated lower pain levels for both oral diclofenac (p=0.015) and topical (p<0.0001) versus placebo, but no difference between oral and topical diclofenac (p=0.67).

The authors reported that for the first PRP, all three groups had lower mean pain scores at 15 minutes after treatment compared with during treatment (p≤0.0003) and that mean pain scores were higher during the second compared with the first PRP for the oral diclofenac (p=0.02) and placebo (p=0.05) groups. They found no significant rate difference for any side effect between groups.

When given in a single dose, oral diclofenac is an effective pretreatment analgesic agent for reducing the pain experienced during PRP for PDR, the authors concluded.

Source: Zakrzewski PA, O’Donnell HL, Lam WC. Oral versus topical diclofenac for pain prevention during panretinal photocoagulation. Ophthalmol 2009;116(6):1168-1174.

Incidence of Endophthalmitis Following 20- and 25-Gauge Pars Plana Vitrectomy
This retrospective, comparative case series was conducted to compare the incidence rate of endophthalmitis after sutureless 25-gauge versus sutured 20-gauge pars plana vitrectomy (PPV) on a large cohort of patients operated with a standardized perioperative anti-infection protocol. Participants consisted of consecutive patients who underwent 20- or 25-gauge PPVs at a single center over a multi-year period.

A total of 3,597 consecutive PPVs were analyzed (patients with a pre-PPV diagnosis of endophthalmitis, PPVs performed for implantation of drug delivery devices or 25-gauge PPVs with all sclerotomies sutured closed were excluded). Patients with ≥1 week of follow up were divided into two study groups by sclerotomy status at the end of surgery: the 20-gauge group had three sutured 20-gauge sclerotomies and the 15-gauge group had ≥1 unsutured 25-gauge sclerotomy. Endophthalmitis was defined by clinical criteria independent of microbiological results and the main outcome measure was the incidence of endophthalmitis compared between 25- versus 20-gauge groups.

Of 3,372 PPV surgeries meeting inclusion and exclusion criteria, 1,948 and 1,424 surgeries were 20- and 25-gauge PPVs, respectively. Average age (± standard deviation) of patients was 54.6 (±22.6) and 64.4 (±16.5) years in the 20- and 25-gauge PPV groups, respectively (p<0.0001). It was observed that median post-PPV follow up was not significantly different between the two groups (12.5 vs 13.0 months; p=0.69). Endophthalmitis was noted in 1 patient (0.07%; 95% confidence interval, 0%-0.21%) from the 25-gauge group and none in the 20-gauge group (p=0.42; Fisher exact test, 2-tailed). Additionally, the use of air/gas endotamponade (p<0.0001) and intravitreal triamcinolone (p<0.001) was more common in 25- versus 20-gauge PPV.

The incidence of endophthalmitis was low in both groups and no significant difference in the incidence of endophthalmitis was evident between sutureless 25-gauge and sutured 20-gauge PPV. It was concluded that a careful perioperative anti-infection protocol may reduce 25-gauge PPV endophthalmitis risk to that of 20-gauge PPV.

Source: Hu AY, Bourges JL, Shah SP, et al. Endophthalmitis after pars plana vitrectomy. Ophthalmol 2009;116(7):1360-1365.

Surgical Outcomes of Epiretinal Membranes in Pediatric Eyes
Investigators in this study conducted a retrospective review of 11 pediatric eyes to determine the surgical outcomes of epiretinal membranes associated with combined hamartoma of the retina and retinal pigment epithelium after pars plana vitrectomy and membrane peeling with or without assistance of autologous plasmin enzyme. They performed preop and postop assessments of visual function and retinal architecture by indirect ophthalmoscopy, optical coherence tomography imaging, fundus photography and measurement of visual acuity.

The mean age of the patients was 4.6 years (range, 1-14) and the mean follow up was 15.6 months (range, 6-42 months). The investigators observed that the lesions were located solely in the macula in 8 of 11 (73%) patients and in the macula and posterior pole in 3 of 11 (27%) patients. Of the 11 eyes, they preoperatively injected 6 with autologous plasmin enzyme to assist in the removal of the posterior hyaloid. According to the investigators, all 11 patients (100%) had complete macular reattachment postoperatively, 8 of 11 (73%) showed improved visual acuity postoperatively and 3 of 11 showed stabilized vision. Eight eyes required only one surgery. Moreover, 4 eyes (36.6%) had recurrences of epiretinal membrane and 3 of these eyes required additional surgery. Of the eyes with preoperative plasmin injection, 4 of 6 (66%) showed an improvement in visual acuity, whereas 2 of 6 (33%) showed stabilization of visual acuity. Four of 5 without plasmin showed visual improvement, and 1 of 5 had stabilization of vision.

The investigators concluded that in the pediatric population, pars plana vitrectomy with membrane peeling with or without the use of autologous plasmin enzyme for epiretinal membrane associated with combined hamartomas of the retina and retinal pigment epithelium can result in improved retinal architecture and visual acuity. They assert that visual acuity may improve despite recurrence of the epiretinal membrane.

Source: Cohn AD, Quiram PA, Drenser KA, et al. Surgical outcomes of epiretinal membranes associated with combined hamartoma of the retina and retinal pigment epithelium. Retina 2009;29(6):825-830.

Evaluation of Intravitreal Microplasmin Given Before Vitrectomy for Vitreomacular Traction Maculopathy
To evaluate the safety and preliminary efficacy of four doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy, researchers conducted a multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial that included 60 patients enrolled into 6 successive cohorts.

As intervention, the researchers administered a single intravitreal injection of microplasmin at 1 of 4 doses (25, 50, 75 or 125 µg in 100 µl) either 1 to 2 hours or 7 days before planned pars plana vitrectomy. Main outcome measures for safety included a complete ophthalmologic examination, fundus photography, fluorescein angiography, Humphrey visual fields and electrophysiology. Main outcome measure for efficacy included posterior vitreous detachment (PVD) induction as assessed by B-scan ultrasound and ease of PVD induction at the time of victrectomy.

The study researchers found that the use of microplasmin led to a progressively higher incidence of PVD induction on ultrasonography with increasing time exposure. They observed a PVD before surgery with 25µg microplasmin in 0, 2 and 5 patients with increasing exposures (2 hours, 24 hours, 7 days). Also, they observed a PVD before surgery by ultrasound with increasing dose (15µg, 0; 50µg, 1; 75µg, 2; 125 µg, 3. At surgery with a 125-µg dose, however, these patients had a discontinuous layer of vitreous present on the retinal surface resulting from the induction of an anomalous PVD in the form of vitreoschisis. According to the researchers, one retinal detachment developed shortly after administration of microplasmin, while two developed after surgery. No other safety concerns were reported.

Results from this initial clinical trial evaluating intravitreal microplasmin show the drug to be well tolerated and capable of inducing a pharmacologic PVD in some patients. Evaluation of microplasmin in larger controlled trials is warranted.

Source: de Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy. Ophthalmol 2009;116(7):1349-1355.

Evaluation of 25-gauge Vitrectomy for Vitreoretinal Conditions in Children
The investigators of this retrospective study evaluated the feasibility and safety of 25-gauge vitrectomy for various vitreoretinal indications in 56 eyes of 49 children (16 girls and 33 boys) in the pediatric population.

They studied consecutive patients aged 18 years or less undergoing vitrectomy for various vitreoretinal indications over a 5-year period, during which two different surgical techniques were used: a modified, 25-gauge approach in which the sclerotomies and conjunctiva were sutured for most children under the age of 1 year, and a transconjunctival 25-gauge approach for older children.

Intraoperative unplanned events or complications included conversion to 20-gauge vitrectomy (4), conversion of one port to a 20-gauge sclerotomy (2), suspected lens damage (1) and intraoperative bleeding from a vascular ridge (1). Postoperative complications included cataract (5), rhegmatogenous retinal detachment (4) and vitreous hemorrhage (3). The investigators noted that the four retinal detachments were either recurrent or occurred in eyes with complex ocular pathology and did not believe them to be related to the surgical technique. There were no cases of postoperative hypotony requiring intervention, choroidal detachment, endophthalmitis or sclerotomy-related retinal breaks.

In light of their research findings, the investigators concluded that 25-gauge vitreoretinal techniques can be used in various pediatric vitreoretinal conditions and facilitate easy access to small spaces in the pediatric eye. To avoid postoperative hypotony, a modified technique is recommended for younger babies in which the conjunctiva and sclera is sutured.

Source: Gonzales CR, Singh S, Schwartz SD. 25-gauge vitrectomy for pediatric vitreoretinal conditions. Br J Ophthalmol 2009;93(6):787-790.

Speed of ROP Diagnosis with Standard Indirect Ophthalmoscopy vs. Telemedicine
The authors of this prospective, comparative study sought to compare the speed of retinopathy of prematurity (ROP) diagnosis using standard indirect ophthalmoscopy with that of telemedicine and determined that telemedicine has the potential to alleviate the time commitment for ophthalmologists who manage ROP.

Three study examiners (2 pediatric retinal specialists and 1 pediatric ophthalmologist) conducted ROP diagnosis via standard indirect ophthalmoscopy and telemedicine. Each examiner performed: 1) standard ophthalmoscopy on 72 to 150 consecutive infants at his respective institution and 2) telemedical diagnosis on 125 consecutive de-identified retinal image sets from infants from an at-risk population. They measured time for ophthalmoscopic diagnosis in 2 ways: 1) time spent by the examiner at the infant's bedside and 2) mean total time commitment per infant. Time for telemedicine diagnosis was recorded by computer time stamps in the web-based system. For each examiner, nonparametric statistical analysis (Mann–Whitney U test) was used to compare the distribution of times for examination by ophthalmoscopy versus telemedicine.

According to the study authors, mean (± standard deviation [SD]) times for ophthalmoscopic diagnosis ranged from 4.17 (± 1.34) minutes to 6.63 (±2.28) minutes per infant. Additionally, mean (± SD) times for telemedicine diagnosis ranged from 1.02 (±0.27) minutes to 1.75 (±0.80) minutes per infant and telemedicine was significantly faster than ophthalmoscopy (p<.0001). They reported that the total time commitment by ophthalmologists performing bedside ophthalmoscopy for ROP diagnosis, including travel and communication with families and hospital staff, was 10.08 (±2.53) minutes to 14.42 (±2.64) minutes per infant.

The authors determined that the ophthalmologist time requirement for telemedical ROP diagnosis is significantly less than that for ophthalmoscopic diagnosis and that additional time requirements associated with bedside ROP diagnosis increased this disparity.

Source: Richter GM, Sun G, Lee TC, et al. Speed of telemedicine vs ophthalmoscopy for retinopathy of prematurity diagnosis. Am J Ophthalmol 2009;148(1):136-142.