2.3.0.0 Treat­ment

Two of the main mo­ti­va­tions for screen­ing for di­a­bet­ic retinopa­thy are to pre­vent loss of vi­sion and to in­ter­vene with treat­ment when vi­sion loss can be pre­vented or re­versed.

Pho­to­co­ag­u­la­tion Surgery

Two large tri­als, the Di­a­bet­ic Retinopa­thy Study (DRS) in pa­tients with PDR and the Early Treat­ment Di­a­bet­ic Retinopa­thy Study (ETDRS) in pa­tients with mac­u­lar edema, pro­vide the strongest sup­port for the ther­apeutic benefits of pho­to­co­ag­u­la­tion surgery. The DRS (96) showed in 1978 that panreti­nal pho­to­co­ag­u­la­tion surgery re­duced the risk of se­vere vi­sion loss from PDR from 15.9% in untreat­ed eyes to 6.4% in treat­ed eyes with the great­est benefit ratio in those with more ad­vanced base­line dis­ease (disc neovas­cu­larization or vit­re­ous hem­or­rhage). In 1985, the ETDRS also verified the benefits of panreti­nal pho­to­co­ag­u­la­tion for high-‍risk PDR and in older-‍onset pa­tients with se­vere non­pro­lif­er­a­tive di­a­bet­ic retinopa­thy or less-than-high-‍risk PDR. Panreti­nal laser pho­to­co­ag­u­la­tion is still com­monly used to man­age com­pli­ca­tions of di­a­bet­ic retinopa­thy that in­volve reti­nal neo-vas­cu­larization and its com­pli­ca­tions.

Anti–Vas­cu­lar En­dothe­lial Growth Fac­tor Treat­ment

Re­cent data from the Di­a­bet­ic Retinopa­thy Clin­i­cal Re­search Net­work and oth­ers demon­strate that in­trav­it­re­al in­jec­tions of anti–vas­cu­lar en­dothe­lial growth fac­tor (anti-‍VEGF) agent, specif­i­cal­ly ranibizum­ab, re­sulted in vi­su­al acu­ity out­comes that were not in­fe­ri­or to those ob­served in pa­tients treat­ed with panreti­nal laser at 2 years of fol­low-‍up (97). In ad­di­tion, it was ob­served that pa­tients treat­ed with ranibizum­ab tend­ed to have less pe­riph­er­al vi­su­al field loss, fewer vit­rec­to­my surg­eries for sec­ondary com­pli­ca­tions from their pro­lif­er­a­tive dis­ease, and a lower risk of de­vel­oping di­a­bet­ic mac­u­lar edema. How­ev­er, a po­ten­tial draw­back in using anti-‍VEGF ther­a­py to man­age pro­lif­er­a­tive dis­ease is that pa­tients were re­quired to have a greater num­ber of vis­its and re­ceived a greater num­ber of treat­ments than is typ­i­cal­ly re­quired for man­age­ment with panreti­nal laser, which may not be op­ti­mal for some pa­tients. Other emerg­ing ther­a­pies for retinopa­thy that may use sus­tained in­trav­it­re­al de­liv­ery of phar­ma­co­log­ic agents are cur­rently under in­ves­ti­ga­tion. The FDA ap­proved ranibizum­ab for the treat­ment of di­a­bet­ic retinopa­thy in 2017.

While the ETDRS (98) es­tab­lished the benefit of focal laser pho­to­co­ag­u­la­tion surgery in eyes with clin­i­cally significant mac­u­lar edema (defined as reti­nal edema lo­cat­ed at or with­in 500 μm of the cen­ter of the mac­u­la), cur­rent data from well-‍de­signed clin­i­cal tri­als demon­strate that in­trav­it­re­al anti-‍VEGF agents pro­vide a more ef­fective treat­ment reg­i­men for cen­tral-‍in­volved di­a­bet­ic mac­u­lar edema than monother­a­py or even com­bi­na­tion ther­a­py with laser (99-101). There are cur­rently three anti-‍VEGF agents com­monly used to treat eyes with cen­tral-‍in­volved di­a­bet­ic mac­u­lar ede­ma-­be­va­cizum­ab, ranibizum­ab, and afliber­cept (77).

In both the DRS and the ETDRS, laser pho­to­co­ag­u­la­tion surgery was benefi- cial in re­duc­ing the risk of fur­ther vi­su­al loss in af­fected pa­tients but gen­er­ally not beneficial in re­vers­ing al­ready di­min­ished acu­ity. Anti-‍VEGF ther­a­py im­proves vi­sion and has re­placed the need for laser pho­to­co­ag­u­la­tion in the vast ma­jor­i­ty of pa­tients with di­a­bet­ic mac­u­lar edema (102). Most pa­tients re­quire near-‍monthly ad­min­is­tra­tion of in­trav­it­re­al ther­a­py with anti-‍VEGF agents dur­ing the first 12 months of treat­ment, with fewer in­jec­tions need­ed in sub­se­quent years to main­tain re­mis­sion from cen­tral-‍in­volved di­a­bet­ic mac­u­lar edema.

Ad­junc­tive Ther­a­py

Low­er­ing blood pres­sure has been shown to de­crease retinopa­thy pro­gres­sion, al­though tight tar­gets (sys­tolic blood pres­sure <120 mmHg) do not im­part ad­di­tional benefit (83). ACE in­hibitors and ARBs are both ef­fective treat­ments in di­a­bet­ic retinopa­thy (103). In pa­tients with dys­lipi­demia, retinopa­thy pro­gres­sion may be slowed by the ad­di­tion of fenofibrate, par­tic­u­larly with very mild non­pro­lif­er­a­tive di­a­bet­ic retinopa­thy at base­line (81,104).