August Literature Round Up

Vitrectomy without Laser Treatment or Gas Tamponade for Macular Detachment Associated with an Optic Disc Pit

[published online ahead of print January 4, 2012]. Hirakata A, Inoue M, Hiraoka T, McCuen BW. Ophthalmol. 2012;119(4):810-818.

Though often asymptomatic and incidental, optic disc pits can be complicated by serous macular detachments and a schisis-like separation of the inner and outer retina. There is controversy in the treatment of optic disc pit maculopathy. Currently treatments can include the use of peripapillary laser to create a barrier between the optic disc and the potential fluid space in the macula. 

Other treatments include varying combinations of vitrectomy, induction of a posterior vitreous detachment (PVD), laser photocoagulation, and internal gas tamponade. Less commonly advocated treatments include internal gas tamponade alone and macular scleral buckling. 

This author group previously reported on the efficacy of vitrectomy with PVD induction and gas tamponade without laser treatment in managing macular detachments associated with optic disc pits. Although the success rate of reattachment was high, complete successful reattachment took almost 1 year after surgery.

Thus, the authors postulated that gas tamponade might not be necessary, as gas was resorbed long before successful reattachment. The elimination of intraocular gas tamponade removes potential complications of fluid-air exchange as well as the need for postoperative facedown positioning.   

This noncomparative, retrospective, interventional case series aimed to evaluate the clinical outcomes of vitrectomy without gas tamponade or laser photocoagulation at the margin of the optic nerve when treating optic disc pit-associated macular detachments. All eyes were evaluated with OCT.

Eight eyes from 8 patients (ages 8 to 56 years) with optic disc pit-associated macular detachments were followed for 10 to 46 months after surgery (mean 26 months). Twenty-gauge vitrectomy was performed on 3 eyes and 25-gauge vitrectomy was performed on 5 eyes. PVD was induced with the intention of releasing vitreous traction at the optic disc pit. 

Preoperative vision ranged from 20/20 to 20/300 (mean 20/67), with a duration of symptoms from 2 to 35 months. Complete retinal attachment was achieved in 7 of 8 eyes after initial treatment, where the postoperative OCT showed an acute reduction of inner schisis-like separation adjacent to the disc and a gradual decrease in outer retinoschisis-like separation. 

Macular detachment decreased gradually, with complete macular attachment ranging from 6 to 16 months (mean 12 months). The corresponding visual acuity also improved postoperatively, and all 7 patients had final best-corrected visual acuity (BCVA) of 20/30 or better.    

One patient did not reattach with vitrectomy without laser or gas tamponade and required a repeat surgery with internal limiting membrane (ILM) peel, subretinal fluid drainage, gas tamponade, and peripapillary laser. Reattachment was achieved 24 months after the initial surgery.

The authors postulate that peripapillary vitreous traction in patients without a PVD is the trigger for schisis-like separation, and perivascular spaces around the pit allow for the passage of fluid into the retina, causing maculopathy. Therefore, the release of anterior-posterior vitreous traction would structurally address the principal trigger for the maculopathy.   

Relevance to patients:  There are many nuances in the treatment for optic nerve pit associated macular detachments.  This article presents a possible alternative to the conventional method for treatment of this condition. 

One-Year Outcomes of the DA VINCI Study of VEGF Trap-Eye in Eyes with Diabetic Macular Edema

[published online ahead of print April 25, 2012].

Do DV, Nguyen QD, Boyer D, et al; DA VINCI Study Group.
Ophthalmol. 2012;119(8):1658-1665.

Diabetic macular edema is the leading cause of vision loss due to diabetic retinopathy. A number of recent clinical trials have demonstrated the potential of intravitreal anti-VEGF agents to effectively reduce diabetic macular edema and improve visual acuity. The DA VINCI study is a randomized, double-masked, phase 2 clinical trial that compared various doses and dosing regimens of VEGF Trap-Eye with laser photocoagulation for the treatment of eyes with diabetic macular edema.

There were 5 possible VEGF Trap-Eye treatment regimens in the study: 0.5 mg every 4 weeks (0.5q4); 2 mg every 4 weeks (2q4); 2 mg every 8 weeks after 3 initial monthly doses (2q8); 2 mg dosing as needed after 3 initial monthly doses (2PRN); or macular laser photocoagulation.

VEGF Trap-Eye groups responded favorably over 52 weeks compared with the laser group in visual acuity, reduction in retinal thickness, and in severity of diabetic retinopathy. The findings were consistent with those reported previously at 24 weeks. Mean BCVA improved by 11.0 letters in the 0.5q4 group, 13.1 letters in the 2q4 group, 9.7 letters in the 2q8 group, 12.0 letters in the 2PRN group, and decreased by 1.3 letters in the laser group (P = .001 vs laser).

A gain of 15 or more ETDRS letters was achieved in 40.9% (P = .0031), 45.5% (P = .0007), 23.8% (P = .1608), and 42.2% (P = .0016) for the VEGF Trap-Eye groups vs 11.4% for laser. Mean central retinal thickness as determined by OCT was reduced in the VEGF Trap-Eye groups by 165.4 µm, 227.4 µm, 187.8 µm, and 180.3 µm vs an increase in retinal thickness of 58.4 µm in the laser group (P < .001 vs laser).

At week 52, 40%, 31%, 64%, and 32% of the 0.5q4, 2q4, 2q8, and 2PRN VEGF Trap-Eye groups, respectively, had an improvement in their diabetic retinopathy severity score, compared with 12% in the laser group.

Adverse events in the trial were similar to those described in therapeutic trials of other anti-VEGF agents. Two eyes developed injection-related endophthalmitis. Systemic adverse events such as hypertension and congestive heart failure were generally attributed to the patient’s underlying medical condition.

Relevance to Patients: This recent study looked at the use of Aflibercept (Eylea®),  also known as VEGF Trap- Eye, for the treatment of diabetic macular edema.  Aflibercept is currently approved for the treatment of wet macular degeneration but has also shown promise in reducing macular edema and improving visual acuity. 

Photoreceptor Damage and Foveal Sensitivity in Surgically Closed Macular Holes: An Adaptive Optics Scanning Laser Ophthalmoscopy Study

[published online ahead of print April 23, 2012]. Ooto S, Hangai M, Takayama K, Ueda-Arakawa N, Hanebuchi M, Yoshimura N. Am J Ophthalmol. 2012;154(1):174-186.e2

The success rate of anatomic closure of macular holes (MHs) after vitrectomy, internal limiting membrane (ILM) peel, and intraocular gas is high. However, successful closed macular holes without concurrent satisfactory visual recovery remains problematic for some patients. There is interest in finding pre- and postoperative indicators for successful visual recovery after MH repair.

Recent studies with OCT have shown associations of disrupted photoreceptor IS/OS junction and postoperative visual dysfunction. This prospective interventional case series takes this research a step further. The series looks at photoreceptor structure using adaptive optics scanning laser ophthalmoscopy (AO SLO) to evaluate decreased cone density and areas of cone loss; it then correlates findings with visual function measured by microperimetry (MP-1; NIDEK, Padova, Italy) and visual acuity. They also correlated findings from AO SLO and spectral-domain OCT (SD-OCT).

Twenty-one eyes of 19 patients with idiopathic full-thickness macular holes (stages 2 to 4) underwent 23-gauge vitrectomy. Either triamcinolone acetonide (8) or 0.05% indocyanine green (ICG) dye (13) ILM peel was performed, followed by a fluid-gas exchange with 25% sulfur hexafluoride (SF6) and facedown positioning for 7 days. All patients had anatomically closed macular holes postoperatively. Fifteen nonoperative normal patients were used as controls.

AO SLO was used to obtain both mean cone density and mean extent of dark area (absence of cones) in square millimeters. When compared with controls, postoperative cone density was significantly less: 19,650 cones/mm2 vs 31,775 cones/mm2 respectively (P = .003). The dark areas measured 0.203 +/- 0.222 mm2 compared with 0 in normal eyes.

Both preoperative (P = .024) and postoperative (P < .001) visual acuity correlated with postoperative cone density. Lower cone density and higher cone loss area correlated with poorer visual acuity. Foveal sensitivity, measured by fundus monitoring microperimetry, also correlated with cone density and cone loss area.

SD OCTs were obtained pre- and postoperatively. IS/OS junction reflectivity, as measured by intensity on gray-scale relative to unaffected peripheral macula, was used to determine the mean diameter of decreased reflectivity; this measured the structural disruption of the IS/OS junction on SD OCT.

The OCT also demonstrated that lower cone density correlated with thinner inner and outer segments (P = .014), but did not correlate with thickness of the outer nuclear layer. There was a correlation between cone loss area (P = .13) and decreased IS/OS reflectivity size and a trend toward correlation between decreased IS/OS reflectivity size (P = .156) and cone density. 

Relevance to patients: Macular hole surgery can improve vision significantly for many patients. However, there are cases where the visual outcome is less than satisfactory. In the future, adaptive optics scanning laser ophthalmoscopy may provide an adjunct to help predict visual recovery and retinal function in patients with macular holes who are undergoing surgery. 

Prediction of Proliferative Vitreoretinopathy after Retinal Detachment Surgery: Potential of Biomarker Profiling. 

[published online ahead of print April 30, 2012]. Ricker LJAG, Kessels AGH, De Jager W, Hendrikse F, Kijlstra A, la Heij EC. Am J Ophthalmol. 2012;154(2):347-354.e2.

Proliferative vitreoretinopathy (PVR) remains the most common reason for redetachment after retinal detachment repair. As new prophylactic therapies emerge to prevent PVR formation, high-risk subgroups need to be identified to improve the risk-to-benefit ratio of adjunctive treatments. Various cytokines have been implicated in contributing to the development of PVR. This study attempts to evaluate the potential for biomarker profiling in identifying this specific subgroup. 

This retrospective case-controlled study evaluated undiluted subretinal fluid samples collected from scleral buckle surgeries for primary rhegmatogenous retinal detachment repairs. These detachments had a maximum PVR grade of C1 and greater than 1 quadrant involvement. Of the 306 samples collected, 45 patients redetached secondary to PVR.

Twenty-four samples were excluded because of low sample volume or contamination (9), late-developing PVR (6), preoperative vitreous hemorrhage (4), preoperative trauma (4), or preoperative cryotherapy (1). 

Twenty-one samples were compared with control samples from patients who did not redetach. On average, 86% had macula-off detachments, 81% had intraocular gas injections, 71% had intraoperative cryotherapy, and 33% were pseudophakic.

Multiplex immunoassays (Luminex; Austin, Texas) were used. These contained antibody-coated microspheres incubated with subretinal fluid along with the 50 potential biomarkers of interest.

The biomarkers of interest included various interleukins (ILs), growth factors, chemokines, adhesion molecules, adipokines, proteases, and inhibitors. Researchers analyzed the correlation between concentrations of biomarkers and clinical preoperative and intraoperative risk factors for PVR. 

Eighteen biomarkers were shown to be significantly different between the PVR group and case controls. The markers included IL-1a, IL-2, IL-3, IL-6, IL-11, macrophage migration inhibitory factor (MIF), chemokine (C-C motif) ligand 2, CCL3, CCL11, CCL17, CCL18, CCL19, CCL22, chemokine (C-X-C motif) ligand 10, cathepsin S, adiponectin, and intercellular adhesion molecule-1. 

The only clinical variable that was an independent predictor of postoperative PVR development was preoperative PVR. The combination of 3 biomarkers: CCL22, IL-3, and MIF in conjunction with preoperative PVR was the best predictor for postoperative PVR redetachment.

The model was able to predict the outcome for PVR redetachment in 94% of cases, with a sensitivity of 94.1% and specificity of 94.2%.

Relevance to patients: The most common cause of retinal detachment surgery failure is proliferative vitreoretinopathy. Biomarker profiling may be a way to help predict patients who may be at higher risk for this complication.