There is no increased risk of tractional retinal detachment (TRD) associated with anti-VEGF (vascular endothelial growth factor) intravitreal injection only, compared with laser-only therapy, nor with 6 months or longer of loss to follow-up in patients with proliferative diabetic retinopathy (PDR), according to a new US-based case-control study.
“One of the primary concerns in selecting intravitreal injections for primary treatment of PDR is the risk of the patient not following up, the duration of the intravitreal-injection treatment effect not being long enough, and the patient returning later with advanced PDR causing a tractional detachment,” write Jonathan C. Tsui, MD, a vitreoretinal fellow physician and surgeon at the Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues, in JAMA Ophthalmology.
However, they note, “We were not able to corroborate this idea with our study results.”
In an accompanying commentary, Jennifer Sun, MD, and Danni Liu, MSPH, say that limitations in physicians’ clinical decision-making may have determined choice of specific treatments for eyes at higher risk of progression to TRD, and this contributed to why the study did not identify a significant association between TRD and prior anti-VEGF treatment.
“Patients in this cohort at higher risk of TRD were less likely to be treated with anti-VEGF therapy alone,” say Sun, from Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, and Liu, from the Jaeb Center for Health Research, Tampa, Florida.
They add that selection bias might also explain why eyes that received the combination of laser and intravitreal injection were more likely to develop TRD than eyes treated with laser alone. “It seems plausible that combination therapy was used more frequently in eyes at higher risk of TRD,” they write.
Higher Risk for Retinal Detachment With Intravitreal Injections Only Investigated
The study aimed to shed light on the effect of different treatment interventions for PDR and their associations with later TDR, a severe complication of proliferative disease.
Interventions comprised pan-retinal photocoagulation (laser treatment) and anti-VEGF intravitreal injections, which regress retinal neovascularization and decrease risk of vision loss. Researchers also determined the effect on TRD, if any, of a 6-month or longer period of loss to follow-up when the patient received no eye care.
Despite available therapies, the authors note that “still far too many patients with PDR progress to TRD.” They add that recent studies show the importance of follow-up on eye-sight outcomes of anti-VEGF-treated diseases.
They also point out that there is some debate around whether a one-off intravitreal injection (compared with laser therapy) has time-limited effects, which is particularly concerning given the number of patients who do not return for follow-up checks.
Patients with PDR often have systemic comorbidities and are at high risk of noncompliance with follow-up and other management recommendations, Sun and Liu note in their commentary, stressing the importance of understanding any association between the two.
Each treatment was administered separately or in combination. There were two primary exposures of interest: firstly, PDR treatment history (anti-VEGF-injection only, laser only, both, or neither), and secondly, patients who had a 6-month or longer period without any eye care.
A total of 214 patients with PDR and TRD (mean age 55.6 years, 53.7% women) were matched in a 1:5 ratio to 978 PDR-only (did not progress to TRD) control participants (mean age 65.6 years, 51.8% women).
No Significant Association Seen With Injection Only, Nor LTFU
Among those patients who went on to develop TRD, 32.2% were treated with laser only, 7.9% with injection only, and 18.2% both, and 41.6% had no prior treatment.
By comparison, among patients in the PDR-only group who did not experience a TRD, 21.2% received laser only, 8.5% received injection only, 5.8% received both, and 64.5% received no treatment.
After adjusted analysis, no difference in odds of TRD for patients who received injection only compared with patients who received laser only was found (adjusted OR [aOR], 0.56; 95% CI, 0.27 – 1.14).
Receiving both injection and laser therapies was related to a higher odds of TRD compared with those who received laser only (aOR, 2.33; 95% CI, 1.21 – 4.48), while patients who received no treatment had a lower odds of TRD (aOR, 0.46; P < .001 for treatment category).
Similarly, no difference was seen in the odds of TRD between those who were lost versus or not lost to follow-up for 6 months or longer (aOR, 0.72, P = .11).
However, loss to follow-up was observed in 50% or more of both the TRD and non-TRD subgroups.
“We need better ways to ensure that patients at risk of vision loss from diabetic retinopathy have consistent and regular ophthalmic follow-up,” Sun and Liu point out.
“Although it is possible that all the untreated eyes in the non-TRD group had mild PDR that did not warrant treatment, the fact that more than 40% of eyes that developed TRD remained untreated speaks to the challenges in treatment delivery that are faced by many patients with PDR globally,” they add.
Recognizing the importance of novel therapies for PDR, Sun and Liu stress that “solutions to the problems of loss to follow-up and undertreatment in patients with PDR are sorely needed and would have enormous positive public health impact.”
Tsui and colleagues agree. “Loss to follow-up rates continue to remain high in patients with PDR, which can contribute to substantial vision loss regardless of treatment regimen,” they conclude.
JAMA Ophthalmol. Published online December 1, 2022. Abstract, Commentary
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