THE LATEST PUBLISHED RESEARCH

Stroke Development and RVO
To investigate the risk of stroke development following the occurrence of retinal vein occlusion (RVO), data were collected from Taiwan National Health Insurance Research Database, which comprises 1073,891 random subjects from 23 million Taiwan residents. The retrospective, nationwide, population-based administrative database study cohort comprised of all patients with a first-time diagnosis of either central or branch RVO from January 1999 to December 2001 (n=350). The comparison cohort comprised randomly selected patients (n=2,100) matched with the study group for age, gender and the date of ambulatory care visit.

Each sampled patient was tracked for five years and Cox proportional hazard regressions were utilized to compute the five-year stroke-free survival rate after adjusting for possible confounding factors.

Stroke developed in 35.1% and 19.9% of RVO patients and comparison groups, respectively. After adjusting for demographic characteristics and comorbidities, RVO was not associated with an increased risk of stroke development (adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.65 to 1.57) among subjects of any age. RVO patients aged 60 to 69 years did, however, have a 2.34-fold (95% CI, 1.05 to 5.24) higher risk of suffering a stroke. Possible causes for this include an actually increased risk of stroke development in the 60- to 69-year group, chance finding, the presence of selection biases, small numbers of stroke patients in the <50 and 50 to 59 age groups or a lack of power in the > or = 70-year group.

Source: Ho J, Liou SW, Lin HC. Retinal vein occlusion and the risk of stroke development: a five-year follow-up study. Am J Ophthalmol 2009;147(2):283-290.e2.

Removal of Internal Limiting Membrane for Macular Edema Associated with Brand Retinal Vein Occlusion
Japanese researchers examined the medical records of 47 eyes of 47 patients with branch retinal vein occlusion (BRVO)-associated macular edema to compare the results of vitrectomy with internal limiting membrane (ILM) peeling to that without ILM peeling for macular edema associated with BRVO.

To treat the macular edema, a posterior vitreous detachment (PVD) was created, and the ILM was removed in 13 eyes (ILM-removed group), whereas a PVD was created and the ILM was not removed in 34 eyes (ILM-preserved group). The best-corrected visual acuity (BCVA) and the optical-coherence-tomography-determined foveal thickness were obtained preoperatively and at 6 months postoperatively.

The mean postop BCVA was significantly better than the preop BCVA in both the ILM-removed and in the ILM-preserved groups (p = 0.0017 and p = 0.0002, respectively). The fovea was significantly thinner at 1 month after surgery in both groups (p = 0.0007 and p < 0.0001, respectively). The postop improvement of the mean BCVA and the foveal thickness were not significantly different for the two groups at any postop period.

The researchers concluded that because there was no significant difference in the improvement of BCVA between the two groups at 6 months postoperatively, there might be no additional benefit in removing the ILM for BRVO-associated macular edema.

Source: Arai M, Yamamoto S, Mitamura Y, et al. Efficacy of vitrectomy and internal limiting membrane removal for macular edema associated with branch retinal vein occlusion. Ophthalmologica 2009;223(3):172-176.

Morphologic Alterations in RPE Shown on Spectral-domain OCT
Spectral-domain optical coherence tomography showed morphologic alterations in retinal pigment epithelium (RPE) in both eyes of patients with idiopathic central serous chorioretinopathy in this prospective case series. To report the changes seen in the RPE morphology in the asymptomatic eyes of patients with idiopathic central serous-chorioretinopathy (ICSC) using spectral-domain Cirrus high-definition optical coherence tomography (HD-OCT), 17 consecutive patients with unilateral ICSC underwent spectral-domain Cirrus HD-OCT scans for both affected and opposite asymptomatic eye.

The researchers studied 3-D single-layer RPE map in both eyes for morphological alteration, and correlated their findings with clinical presentation, fluorescein angiogram and 5 Line raster scan. 3-D single-layer RPE maps done in 111 healthy volunteers served as control and in patients with ICSC, 3-D single-layer RPE analysis of asymptomatic eyes showed the presence of RPE bumps in 16 (94%) eyes and pigment epithelium detachment (PED) in 2 (11.8%) eyes. The researchers noted that the 5 Line raster scan was normal in all eyes and of 222 normal (control) scans, 18 showed RPE bumps and none showed PED.

Source: Gupta P, Gupta V, Dogra MR, et al. Morphological changes in the retinal pigment epithelium on spectral-domain OCT in the unaffected eyes with idiopathic central serous chorioretinopathy. Int Ophthalmol 2009;Jan. 30 [Epub ahead of print].

Comparison of Retinal Thickness Quantification with Two OCT Systems
The authors of this prospective comparison compared Cirrus Fourier-domain optical coherence tomography (OCT) with Stratus time-domain OCT for imaging retinal diseases and quantifying retinal thickness (RT) of all nine OCT zones, central macular thickness and average macular thickness in eyes with and without macular edema. They measured RT in 120 eyes of 60 patients suspected of having increased retina thickness using both Stratus and Cirrus OCT on the same day. A total of 21 eyes had both 512 x 128 and 200 x 200 Cirrus cube scans performed.

Data from 101 eyes (53 patients) were analyzed; 46 eyes (45.5%) had macular edema on clinical examination (Group 1), whereas 55 eyes (54.5%) had no clinical evidence of macular edema (Group 2). The authors noted modest correlation between all thickness measurements in 909 zones and each group (range of Pearson correlation, 0.51 to 0.89) and average value was significantly greater when measured with Cirrus OCT for all eyes (mean difference, 43.2 µm; p < .0001). There were few measurement differences between different resolution Cirrus cube scans.

Cirrus OCT measures RT approximately 43 µm greater than Stratus OCT, which is likely attributable to Cirrus OCT detection of the outer band of the retinal pigment epithelium versus Stratus OCT detection of the inner/outer segment photoreceptor junction. All zones showed a wide degree of variability in correlation and both Cirrus cube scans provide similar data. The authors note that future studies comparing these systems might consider utilizing average macular thickness values, which reflect macular volume and may provide more consistent measurements.

Source: Kiernan DF, Hariprasad SM, Chin EK, et al. Prospective comparison of Cirrus and Stratus optical coherence tomography for quantifying retinal thickness. Am J Ophthalmol 2009;147:267-275.

Results of Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy
This single-center, randomized clinical trial evaluated laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). Researchers performed laser (panretinal and macular) photocoagulation in each eye of 22 patients with bilaterial treatment-naïve moderate PDR and CSME, then administered IVTA in one randomly assigned eye. They performed best-corrected visual acuity (BCVA), fundus photography and optical coherence tomography at baseline and at months 1, 3, 6, 9 and 12. Changes in BCVA, central macular thickness (CMT) and total macular volume (TMV) were the main outcome measures.

According to the researchers, the mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser-only group (controls) at all study follow-up visits (p<.001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50-2) for the IVTA group was 0.38 (20/50+1) for the controls at baseline and 0.12 (20/25-1) for the IVTA and 0.32 (20/40-1) for the controls at 12 months (p<.001). The mean CMT and TMV were, respectively, 360 µm and 8.59 mm³ for the IVTA group and 331 µm and 8.44 mm³ for the controls at baseline, and 236 µm and 7.32 mm³ for the IVTA group and 266 µm and 7.78 mm³ for the controls at 12 months (p<.001).

The researchers determined that the combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME.

Source: Maia OO, Takahashi BS, Costa RA, et al. Combined laser and intravitreal triamcinolone for proliferative diabetic retinopathy and macular edema: one-year results of a randomized clinical trial. Am J Ophthalmol 2009;147(2):291-297.e2.

Difference in Dose of Intravitreal Bevacizumab for Diffuse Diabetic Macular Edema
In reporting the 12-month anatomic and ETDRS best-corrected-visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin) (1.25 mg or 2.5 mg) in patients with diffuse diabetic macular edema (DDME), the clinical records of 82 consecutive patients (101 eyes) with DDME were reviewed in this interventional, retrospective, multicenter study. A comparison of the two different doses of intravitreal bevacizumab (IVB) was also made.

All patients with a minimum follow up of 12 months (mean 57.6 ± 8.4 weeks) were included in this analysis and patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT) and fluoroscein angiography (FA) at baseline and follow-up visits.

The mean age of patients was 59.7 ± 9.3 years. The mean number of IVB injections per eye was three (range: one to six injections) at a mean interval of 14.1 ± 10.5 weeks. At 1 month, BCVA improved from 20/190, logMAR = 0.97 to 20/85, logMAR 0.62 in the 1.25 mg group, a difference that was statistically significant (p = 0.0001) and this improvement was maintained throughout the 3-, 6- and 12-month follow up. The mean final BCVA at 12 months was 20/76, logMAR = 0.58 (p < 0.001), a statistically significant difference from baseline BCVA. Similar BCVA changes were observed in the 2.5 mg group. The mean central macular thickness (CMT) decreased from 419.1 ± 201.1 µm at baseline to 295.11 ± 91.5 µm at 1 month, 302.1 ± 124.2 µm at 3 months, 313.4.1 ± 96.3 µm at 6 months and 268.2 ± 95.5 µm at 12 months (p<0.0001) in the 1.25 mg group and similar CMT changes were observed in the 2.5 mg group. Adverse events included transient increased intraocular pressure in one eye (1%), and tractional retinal detachment in one eye (1%).

While primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, OCT and FA in DDME at 12 months, there seemed to be no difference in this study's results between IVB at doses of 1.25 mg or 2.5 mg. Additionally, the results suggest the need for at least three injections each year to maintain the BCVA results.

Source: Arevalo JF, Sanchez JG, Fromow-Guerra J, et al. Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol 2009;Feb. 3 [Epub ahead of print]. DOI: 10.1007/s00417-008-1034-x.

Infliximab for Neovascular AMD
Researchers presented their preliminary experience on intravitreal administration of an anti-tumor necrosis factor (TNF) monoclonal antibody for neovascular age-related macular degeneration (AMD) in this prospective, noncomparative series of three patients previously treated with an anti-vascular endothelial growth factor (VEGF) agent.

They administered two intravitreal injections of 0.05 ml containing infliximab in the first (1 and 2 mg, 2 months apart), second (2 mg each, 2 months apart) and third patient (2 mg each, 3 months apart) and assessed best-corrected visual acuity (BCVA) and central foveal thickness (CFT) for up to 7 months. In the first patient, BCVA increased from 20/200 to 20/100 and CFT decreased from 462 to 386 µm, 2 months after the first injection. According to the researchers, the condition was further improved after the second injection (BCVA, 20/40; CFT, 210 µm), but recurrence occurred 7 months post-baseline. In the second patient, BCVA increased from 20/200 to 20/70 and CFT decreased from 512 to 420 and 184 µm, 2 and 4 months post-baseline, respectively. In the third patient, clinical improvement was documented after the first injection and a second injection attributable to recurrence resulted in improvement of BCVA from 20/100 to 20/30 and decrease of CFT from 388 to 282 µm, 2 months after the second injection.

The researchers conclude that their findings, although insufficient to consider "off-label" treatment with intravitreal infliximab, provide in vivo evidence of a pathogenetic link of locally produced and/or acting TNF to neovascular AMD. They believe that a randomized study of consecutive intravitreal injections of infliximab for AMD may be warranted.

Source: Theodossiadis PG, Liarakos VS, Sfikakis PP, et al. Intravitreal administration of the anti-tumor necrosis factor agent infliximab for neovascular age-related macular degeneration. Am J Ophthalmol 2009; Feb. 10 [Epub ahead of print]. DOI: 10.1016/j.ajo.2008.12.006.

Ranibizumab's Effect on Vision Loss and BCVA in Patients with Subfoveal CNV
This interventional case series sought to demonstrate not only prevention of vision loss, but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). The case series involved 138 eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab, age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD and found that intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BCVA and reducing central retinal thickness (CRT).

After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in CRT on optical coherence tomography (OCT), active CNV on fluorescein angiography, in crease of metamorphopsia and loss of BCVA >5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Compared with baseline, main outcome measures were: proportion of eyes gaining ≥15 letters, proportion of eyes losing or gaining <15 letters and change in CRT.

After 24 months, 30% of eyes gained ≥15 letters, 85% lost or gained <15 letters and the mean CRT of 386 ± 145 µm at baseline was significantly reduced to 211 ± 39 µm after 24 months (p = .036). Mean injection number per patient was 5.6 ± 2.9 and 4.3 ± 3.8 from baseline to month 12 and month 12 to 24, respectively. These outcomes were achieved with a low rate of mild ocular adverse effects among patients.

Source: Rothenbuehler SP, Waeber D, Brinkmann CK, et al. Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration. Am J Ophthalmol 2009; Feb. 13 [Epub ahead of print]. DOI: 10.1016/j.ajo.2008.12.005.

Outcomes of Eyes with Severe Open-Globe Injury with No Light Perception After Vitreoretinal Surgery
A cohort of patients with verified no light perception (NLP) following open-globe injury who have recovered vision of light perception (LP) or better were identified and the outcomes of vitreoretinal surgery performed on eyes that were NLP post open-globe injury were evaluated. In this retrospective review of outcomes of secondary vitreoretinal surgery performed at Massachusetts Eye and Ear Infirmary from January 1, 2001 to December 31, 2006 on all cases of open-globe repair (OGR) that had NLP prior to OGR or on the first postop day, 648 cases of OGR were performed.

A total of 88 patients had NLP prior to OGR or on the first postoperative day after OGR, 23 of which (26.1%) spontaneously recovered a vision of light perception (LP) or better and eight of the 23 patients had a secondary vitreoretinal surgery. All eyes that did not undergo vitreoretinal surgery returned to NLP or became phthisical within 7 months. Among the eight eyes that underwent surgery, five had improvement, with vision ranging from hand motion to 20/70. Prognostic indicators for successful surgical outcome were hand motion or better vision prior to vitreoretinal surgery, recover of vision within 5 days of OGR and vitreoretinal intervention within 5 weeks of the initial open-globe injury.

The study authors conclude that patients who have severe open-globe injury and NLP occasionally recover LP or better vision and that these patients may regain useful vision after vitreoretinal surgery if prompt referral and intervention is attempted and if the spontaneous visual recovery occurs within the first week after OGR.

Source: Salehi-Had H, Andreoli CM, Andreoli MT, et al. Visual outcomes of vitreoretinal surgery in eyes with severe open-globe injury presenting with no-light-perception vision. Graefes Arch Clin Exper Ophthalmol 2009; Jan. 27 [Epub ahead of print]. DOI: 10.1007/s00417-009-1035-4.

Retinal Function Following Selective Ophthalmic Artery Chemotherapy Infusion for Retinoblastoma
In this uncontrolled, prospective case series, investigators offered elective ophthalmic artery chemotherapy infusion treatment to patients with advanced retinoblastoma under an IRB-approved protocol as an alternative to enucleation to assess potential retinal viability by electroretinography. They determined that retinal function can persist and even recover following selective ophthalmic artery chemotherapy infusion for retinoblastoma.

The investigators cannulated the ophthalmic artery under fluoroscopic control and directly infused chemotherapeutic agents (melphalan and occasionally carboplatin) at doses resulting in very high local tissue concentrations, but low systemic drug levels. They then examined eyes under anesthesia at 1-month intervals, and re-treated as indicated, up to a maximum of six infusions. Electroretinograms were obtained during examination under anesthesia, using ERG-jet contact lens electrodes and a hand-held mini ganzfeld stimulator. The ERG protocol was similar to ISCEV standards except for briefer adaptation times as necessary to reduce the total anesthesia duration.

In the initial results from the first 10 patients attempted, the investigators reported that nine eyes were successfully cannulated and perfused. ERG data for these nine patients were reported as follows: Follow up ranged from three to 14 months, and often total, retinal detachments were present in many of the treated eyes. While regression of tumor mass and vitreous seeds was observed in nearly all of the patients, retinal detachment occasionally persisted. ERG responses were extinguished in these eyes and eyes with largely attached retinas, notwithstanding the presence of large tumors at baseline, remained free of detachment after treatment. Normal or near-normal ERGs in these eyes were repeatedly obtained and recovery of ERG amplitudes was observed in three patients following treatment.

According to the investigators, further work is indicated to determine optimal dosing regimens, maximal tolerated dosage and subsequent visual function in these patients.

Source: Brodie SE, Gobin YP, Dunkel IJ, et al. Persistence of retinal function after selective ophthalmic artery chemotherapy infusion for retinoblastoma. Documenta Ophthalmologica 2009; Jan. 25 [Epub ahead of print]. DOI: 10.1007/s10633-008-9164-3.