RANIBIZUMAB PLUS PROMPT VS DEFERRED LASER FOR DIABETIC MACULAR EDEMA

The 2-year results of the Diabetic Retinopathy Clinical Research Network Protocol I randomized trial [DRCR Protocol I; Elman MJ et al. Ophthalmology. 2011] demonstrated that treatment with the intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent ranibizumab, with prompt or deferred laser, was more effective than laser alone. However, the 3-year comparison of ranibizumab groups concluded that prompt laser was no better and possibly worse than deferred laser [Elman MJ et al. Ophthalmology. 2012]. The 5-year analysis, presented by John A. Wells III, MD, Palmetto Retina Center, West Columbia, South Carolina, USA, compared the longer-term course of the ranibizumab groups.

Eyes assigned to prompt vs deferred laser needed fewer ranibizumab injections over 5 years (Table 1).

The median number of laser treatments before the 5-year visit was 3 in the prompt laser group vs 0 in the deferred laser group. Prior to the 5-year visit, 0 eyes assigned to prompt laser vs 56% assigned to deferred laser had not received laser treatments.

The estimated mean change in retinal thickening (OCT central subfield [CSF]) at 5 years was −170 with prompt laser vs −162 with deferred laser (estimated difference, −8; 95% CI, −30 to 14; P = .48). Endophthalmitis developed in 1 of 187 eyes (1%; 0.04% per injection) assigned to prompt laser and in 2 of 188 eyes (1%; 0.06% per injection) assigned to deferred laser.

More than half the patients assigned to deferred laser had not received laser therapy through 5 years. Eyes assigned to prompt laser needed fewer injections over 5 years. Few eyes in either group had substantial visual acuity (VA) loss, but about one-third were still thickened.

CHRONIC PERSISTENT CENTRAL-INVOLVED DIABETIC MACULAR EDEMA

Data from the DRCR Protocol I trial showed that 41% of eyes had persistent or recurrent edema (CSF ≥ 250 μm) 2 years after treatment initiation [Elman MJ et al. Ophthalmology. 2011]. Susan B. Bressler, MD, Johns Hopkins University, Baltimore, Maryland, USA, presented an analysis of OCT and VA changes through 3 years among eyes with chronic persistent central-involved diabetic macular edema (CI-DME) 24 weeks after initiating intravitreal ranibizumab (n = 1 17 [38%]; median, CSF = 309 μm). Included patients received ≥ 4 intravitreal ranibizumab injections before the 24-week visit.

Approximately 40% of eyes had chronic persistent CI-DME through 3 years with continued ranibizumab treatment and laser. The cumulative probability of chronic persistent CI-DME decreased over time (85%, 58%, and 42% by years 1, 2, and 3, respectively).

Eyes without chronic persistent CI-DME had better VA outcomes, and substantial loss of VA (≥ 2 lines) was uncommon through 3 years, even for eyes with chronic persistent CI-DME. Among eyes with chronic persistent CI-DME, 45% had VA improvement ≥ 10 letters, and 13% had VA worsening ≥ 10 letters at 3 years.

Dr Bressler concluded that chronic persistent CI-DME may not be as common or as ominous for vision outcomes as previously thought. Caution should be exercised when considering specific approaches for future management of chronic persistent DME.

CURRENT APPROACHES TO MANAGING DR

Jennifer K. Sun, MD, Harvard Medical School, Boston, Massachusetts, USA, discussed current treatment strategies for PDR. Panretinal photocoagulation (PRP) laser is a highly effective treatment for PDR, but it causes serious complications, including destruction of the retina, peripheral and night vision loss, changes in color perception, and burns to the fovea, lens, iris, and cornea.

Dr Sun reviewed studies of the effectiveness of anti-VEGF treatment for DR and the risk of progression or need for PRP (Table 2). Protocol S [NCT01489189] is another study currently underway to assess outcomes of prompt PRP vs intravitreal ranibizumab with deferred PRP for PDR.

New imaging techniques offer improved assessment of DR and response to treatment. Peripheral findings on ultrawide-field fundus photography and angiography allow visualization of the peripheral retina, which may lead to increased DR severity in about 10% of eyes and imply an increased risk of worsening. An upcoming study, Protocol AA [DRCR.net. 2014], will evaluate assessment of DR using ultrawide-field fundus images.

IMPACT OF RECENT CLINICAL TRIALS On PREFERRED PRACTICE PATTERNS

Paul Sternberg Jr, MD, Vanderbilt Eye Institute, Nashville, Tennessee, USA, discussed the potential impacts of recent clinical trials on the 2014 American Academy of Ophthalmology's Preferred Practice Patterns [PPP; American Academy of Ophthalmology. Diabetic Retinopathy PPP-2014. 2014]. According to Dr Sternberg, the recently revised guidelines should be up-to-date, but they may not reflect some recent advances. The highlighted findings and recommendations of the PPP are summarized in Table 3.

The results of recent clinical studies that may affect the 2014 PPP are summarized in Table 4.

The importance of annual screening for DR will increase as the prevalence of DM rises. Dr Sternberg concluded that communication with the primary care physician and emphasis of metabolic control to patients are critical for the management of DR.

MEDICAL TEAM COMMUNICATION CRITICAL FOR OPTIMAL DIABETES EYE CARE

Lloyd Paul Aiello, MD, PhD, Harvard Medical School, Boston, Massachusetts, USA, discussed the importance of coordinating new retinal treatments with primary care providers for patients with DM. Patients with DM should be assessed for the presence, localization, and extent of retinal lesions and retinal thickening and for the risk of progression. The appropriate therapy should be initiated and follow-up maintained.

Glycemic control is critical for the prevention and control of DR. In a 1993 study, patients with controlled blood glucose were found to have 27% less retinopathy development, 78% less retinopathy progression, 47% less severe retinopathy, 23% less macular edema, and 56% less need for photocoagulation. In the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications cohort follow-up, insulin-dependent patients with DM receiving intensive therapy (median HbA_1c, 7.3%) vs conventional therapy (median HbA_1c, 9.1%) had a 62% reduced risk of retinopathy over 7 years [DCCT/EDIC Research Group. JAMA. 2002].

Elevated lipid levels are associated with increased hard exudate and DME development. Other systemic conditions that affect development and progression of retinopathy include blood pressure, pregnancy, renal disease, anemia, and eating and psychological disorders.

Dr Aiello noted that severe DR can exist despite excellent vision. The risk of retinopathy being present when not observed by examination of a non-eye care provider through undilated pupils is approximately 50%. Furthermore, patients with DR are often unaware of their eye disease, a major factor in nonadherence to eye care guidelines and poor vision outcomes [Huang OS et al. Ann Acad Med Singapore. 2009; Schoenfeld ER et al. Ophthalmology. 2001].

A study currently under review by the Joslin Diabetes Center at Harvard Medical School evaluated 2853 patients with DM by telemedicine retinal imaging and asked questions to evaluate their awareness of retinopathy. Ninety-three percent with mild DR and 63% with vision-threatening DR were unaware of their eye disease.

Patient-reported timeliness of follow-up results showed that among all patients, follow-up was not timely in 49% with no DR, 49% with mild DR, and 83% with vision threatening DR. Among those with scheduled visits, follow-up was not timely in 6% with no DR, 5% with mild DR, and 71% with vision-threatening DR.

Dr Aiello concluded that for state-of-the-art DM eye care, full medical team communication is critical and must include the following: identification of individuals with DM, lifelong evaluation and education, optimized systemic factors, identification of complications, timely and appropriate intervention, and evaluation of novel treatment approaches.