As breakthrough therapies and management strategies, along with emerging imaging algorithms, give retina specialists more and better tools for treating retinal disease, investigators continue to push the envelope and take retinal disease management to the next level, as evidenced by the thousands of abstracts presented last month at ARVO 2015 in Denver.

Here we present 10 compelling posters and presentations. They include exploration of the role of  platelet-derived growth factor (PDGF) in the management of age-related macular degeneration (AMD), treatment of central serous chorioretinopathy, an approach to type 2 macular telangiectasia (MacTel) management, novel retinal detachment repair ideas, the importance of wide field retinal imaging and the relationship between vascular endothelial growth factor (VEGF) inhibition and macular atrophy in neovascular AMD treatment. Some of the studies are pre-clinical, others involve established therapies.

After each abstract you’ll find a citation representing the abstract number, which you can use to locate the original report. Disclosures are also noted.

PDGF, VEGF Inhibition

An orally active tyrosine kinase inhibitor that acts against all PDGF and VEGF subtypes stabilized vision  without the need for rescue therapy in a multicenter, early stage trial. Thirty-five patients with wet AMD who had been treated previously received X-82 (Xcovery Vision Inc.) in six different doses, ranging from 50 mg every other day to 300 mg daily. Eighty-nine percent of the 27 subjects who completed the full 24-week study did not require any rescue therapy with ranibizumab (Lucentis, Genentech). Eight subjects—one who received 100 mg, five who received 200 mg and two who received 300 mg—experienced significant reductions in fluid on spectral-domain optical coherence tomography (SD-OCT) within the first few weeks of X-82 initiation.

The investigators said the results suggest a therapeutic effect of the combination anti-VEGF/anti-PDGF X-82 oral pharmaceutical. The drug may offer an alternative delivery mechanism for anti-VEGF and anti-PDGF therapy. All the investigators disclosed commercial relationships with Xcovery.4804

Anti-VEGF therapy may benefit many patients with advanced visual loss from neovascular AMD, a retrospective analysis of 1,410 consecutive cases showed. The authors, noting that most anti-VEGF trials excluded subjects with severe visual loss, aimed to evaluate the efficacy of anti-VEGF intravitreal injections in neovascular AMD patients with advanced visual loss at therapy initiation and identify predictive factors.  

The study involved 134 cases with baseline vision of 20/200 or worse and no other visually limiting eye disease, and followed them for six months; 97 were followed for 12 months. Univariate analysis showed an association between retinal hemorrhage and greater improvement, while intraretinal fluid on OCT was associated with less improvement at 12 months. By multivariate analysis, poorer visual acuity at baseline was associated with greater visual improvement, as was a greater number of injections received.

Larger macular lesion size on fluorescein angiography correlated with worse visual acuity at six but not at 12 months by both univariate and multivariate analyses. Injection medication type did not influence outcome. The authors concluded that the number of injections, macular lesion size and other clinical abnormalities might influence outcomes. They had no relevant relationships to disclose.1503

RTH258 (Alcon) is an anti-VEGF medication given by intravitreal injection that is smaller molecularly than existing anti-VEGF treatments, which may allow greater penetration of ocular tissue and less systemic anti-VEGF exposure. The Phase II OSPREY trial randomized 86 patients with neovascular AMD to repeated doses of RTH258 or aflibercept (Eylea, Regeneron). The trial found that RTH258 was not inferior and was well tolerated. Patients in both groups were comparable in terms of presence of intraocular hemorrhage, subfoveal choroidal neovascularization, subretinal fluid and intraretinal cystoid edema. All of the study participants disclosed relationships with Alcon.4801

As-needed treatment with ranibizumab
can maintain vision improvements in individuals with diabetic macular edema (DME), according to three-year results from an open-label extension of the RIDE/RISE trials. Patients were randomized to monthly ranibizumab 0.3 mg or 0.5 mg, or sham injections. Sham patients crossed over to monthly ranibizumab 0.5 mg after 24 months, and after 36 months participants were eligible to enter the open-label extension (OLE) study of ranibizumab 0.5 mg as needed.

Five hundred patients entered the OLE, receiving an average of 3.8 injections of ranibizumab 0.5 mg annually. Nearly 25 percent of patients did not require any further therapy during the OLE. Of 298 patients followed for more than a year, 19.5 percent required no further treatment. At 36 months, the 0.3 mg ranibizumab group showed an average gain of 12.4 letters in visual acuity, compared with 11.2 letters for the 0.5 mg group Compared to their respective RISE/RIDE baselines. The study co-authors disclosed relationships with Genentech.3145

Chronic Central Serous Chorioretinopathy

Photothermal therapy delivered by micropulse laser is safe and can improve visual acuity in the treatment of central serous chorioretinopathy (CSCR), and may have potential for treatment of other macular disorders, according to a study of 19 eyes using the PASCAL laser (Topcon) using EndPoint Management software. The investigators applied an average of 532 laser spots at 30 percent energy. All patients had persistent CSCR of longer than four months.

Participants received, on average, 2.2 treatments a year to manage recurrent fluid or incomplete resolution. They achieved an average gain of 12 letters at two months and sustained that through 12 months of follow-up. Central macular thickness decreased from 350 to 271 μm.

The investigators concluded that lack of tissue damage allows periodic retreatment without the cumulative scarring of conventional photocoagulation. They said this technique should be tested for the treatment of other macular disorders, and may even be combined with anti-VEGF treatments of macular pathology. All the investigators disclosed relationships with Topcon.5674

The mineralocorticoid receptor antagonists
spironolactone and eplerenone are effective for the treatment of treatment for CSCR, a randomized, placebo-controlled, crossover clinical trial showed. The study reported that spironolactone appeared to have better anatomic outcomes and achieved a faster resolution of subretinal fluid.

The trial included 30 patients with CSCR of at least three-months duration, randomized to three groups:

• 25 mg/day of oral spironolactone for a week then 50 mg/day for three weeks then 50 mg/day oral eplerenone for a month.
• 25 mg/day of oral eplerenone for a week then 50 mg/day for three weeks, then 50 mg/day of oral spironolactone for a month.
• 25 mg/day of oral placebo for a week then 50 mg/day for three weeks, then 50 mg/day oral spironolactone for a month.

The study showed central retinal thickness decreased significantly in Groups 1 and 2. Best-corrected visual acuity (BCVA) improved by 6.2 and 5.8 letters at crossover in Groups 1 and 2, respectively, and remained stable at conclusion. In comparison, BCVA of sham patients decreased without active treatment and then increased by 3.2 and 4.1 letters one and three months after rollover, respectively. The authors also noted that changing treatments from spironolactone to eplerenone did not result in further gains in visual acuity. The authors had no relationships to disclose.1284

Type 2 Macular Telangiectasia

Early results of a ciliary neurotrophic factor (CNTF) implant for treatment of type 2 macular telangiectasia, known as MacTel, have shown no safety issues with the treatment, according to a non-randomized, Phase I, uncontrolled trial of seven patients who completed three years of study. None of the patients had neovascularization secondary to MacTel at enrollment or after three years, and imaging showed no significant progression of any MacTel characteristics. The mean retinal thickness in eyes with the CNTF implant showed a marked increase in ETDRS zones 6-9 (20-23 μm), while the untreated eyes showed less increase of 6-11 μm. By en-face imaging, the key regions of macular pathology did not change in either eye significantly during the trial.

The investigators described an ongoing Phase II trial to further evaluate safety and efficacy of CNTF in MacTel. The study authors had no conflicts to disclose.1815

Repair of Retinal Pathology

An absorbable polyethylene glycol-based synthetic hydrogel sealant has been shown to seal retinal breaks and prevent experimental rhegmatogenous retinal detachment in rabbit eyes without intraocular tamponade. FocalSeal (Focal Inc.) is a liquid that polymerizes under visible xenon illumination, and forms a clear, flexible and adherent hydrogel. The investigators applied FocalSeal to entirely cover iatrogenic retinal breaks in three rabbit eyes and then polymerized the liquid with xenon light. They then performed air-fluid exchange and finished without intraocular tamponade. They did the same procedures in three other eyes but without FocalSeal.

Funduscopy showed that the retinas were reattached in all eyes of the FocalSeal group while all three eyes of the control group resulted in proliferative vitreoretinopathy. The investigators observed FocalSeal on the retinal breaks at one and seven days, but not after one month. None of the investigators had any relationships to disclose.397

Three treatment options exist for rhegmatogenous retinal detachment: scleral buckle (SB), pneumatic retinopexy (PR) or pars plana vitrectomy (PPV). A study of post-procedure quality-of-life outcomes reported that patients who had SB or PR had similar quality-of-life scores, which were higher than patients who had PPV.

Evaluation of retinal detachment surgery outcomes often overlooks quality of life, the authors stated. They administered a modified version of the Visual Function Questionnaire (VFQ-25) by mail or phone to 80 patients: 31 SB, 28 PR and 21 PPV. Composite VFQ-25 scores were 50.49 for patients who had PPV, 78.86 for SB and 81.1 for PR.

The study found no differences for recovery time or postoperative difficulty between the three groups. The study received support from the National Heart, Lung and Blood Institute. The study authors had no other disclosures.5070

Imaging Analytics

A computer-based segmentation algorithm for ultra-widefield angiography can analyze ischemia and leakage in diabetic retinopathy and retinal venous occlusions (RVO). Investigators developed the algorithm to identify areas of leakage and ischemia with co-registration of the two image time points using ultra-widefield angiography by the 200Tx (Optos). They also performed manual segmentation with Image J software to validate the computerized algorithm. They quantified areas of ischemia relative to the overall retinal area, measured by an “ischemic index.” Similarly, they also quantified relative area of leakage, creating a  “leakage index.”

The study included 32 eyes of 32 patients with diabetic retinopathy or RVO. The automated algorithm successfully analyzed all images. All eyes displayed macular and/or peripheral leakage, while only 18 eyes presented with ischemia. The average leakage index was 4.4 percent. Of the 18 eyes with ischemia, the mean ischemic index was 13.7 percent, most of which was peripheral.

Standard angiography may overlook pathology in the retinal periphery, the authors stated. Gaining a better understanding of the location of these features—in the far or mid-periphery or macula—may aid in evaluating disease burden, treatment response and prognosis, but more research is needed to enhance identification of leakage. None of the investigators had any relationship with Optos.3067  RS