There has been little study of loss to follow-up (LTFU) in patients with retinal disease in the setting of anti-vascular epithelial growth factor therapy (anti-VEGF) and panretinal photocoagulation (PRP) treatments. Previous adherence studies have evaluated compliance with annual dilated fundus exams in Medicare beneficiaries with a history of diabetes and chronic eye diseases. These studies have suggested that up to 25% of patients have at most 1 documented dilated fundus exam in a 4-year period.1,2 Given the complications associated with lack of treatment, it is essential that retina specialists continuously monitor LTFU rates and evaluate relevant risk factors. We conducted 2 studies that sought to document LTFU rates post treatment for both proliferative diabetic retinopathy (PDR) and neovascular age related macular degeneration (nAMD) in the tristate region of Pennsylvania, New Jersey, and Delaware. The studies also evaluated several demographic risk factors and their association with LTFU immediately after treatment.
LOSS TO FOLLOW-UP AND RISK FACTORS
To evaluate LTFU, the interval between each procedure and subsequent follow-up visit was measured. Loss to follow-up was defined as at least 1 interval exceeding 12 months duration. Therefore, patients with multiple treatment sessions that required only 1 interval of greater than 12 months were classified as LTFU. Several patient characteristics were also gathered for the analysis. These included age, gender, regional adjusted gross income, distance to clinic, and visual acuity.
Loss to Follow-up Rates
A total of 2,302 patients with PDR and 9,007 patients with nAMD were utilized in the analysis. Loss to follow-up rates immediately post treatment were approximately 22% for patients receiving intravitreal anti-VEGF injection for PDR (Figure 1),3 28% for patients receiving PRP for PDR (Figure 2),3 and 22% for patients receiving anti-VEGF therapy for nAMD (Figure 3).4 These findings are particularly alarming given the relatively conservative definition of LTFU. Indeed, the 5-year Protocol S follow-up study demonstrated that LTFU rates can reach as high as nearly 40% over a 5-year period.5 Another interesting observation is the relatively similar LTFU rates between the 2 diseases. Similar rates have also been observed in RVO and DME. Therefore, one might surmise that the disease is not as important of a predictor of LTFU status.
Age appeared to significantly influence LTFU rates, albeit differently depending on the disease. Younger patients with PDR (≤65 years) had greater LTFU rates (~28%) when compared to older patients (>65 years, ~21%). We believe the disparity in these rates may be heavily influenced by Medicare coverage. Patients with nAMD in our practice had a greater mean age (82 years) and therefore the evaluation of age as a risk factor was less likely to be confounded by insurance status. For these patients, we observed a stepwise increase in LTFU rates as age increased. Rates ranged from less than 20% for patients less than 80 years of age and greater than 30% for patients greater than 90 years of age (Table 1). This could represent an increase in the prevalence of comorbidities that would restrict independent functioning. Given the set treatment schedules, these restrictions could prevent patient compliance.
|AGE, YEARS||FOLLOWED UP, N (%)||LOST TO FOLLOW-UP, N (%)|
|≤80||3,104 (44.3)||583 (29.1)|
|81-85||1,713 (24.5)||458 (22.9)|
|86-90||1,475 (21.1)||567 (28.3)|
|>90||712 (10.2)||395 (19.7)|
|Male||2,411 (34.4)||679 (33.9)|
|Female||4,593 (65.6)||1,324 (66.1)|
|White||6,299 (89.9)||1,606 (80.2)|
|African American||104 (1.5)||39 (1.9)|
|Asian||67 (1.0)||34 (1.7)|
|Other (includes Hispanic, Native American, Pacific Islander)||15 (0.2)||11 (0.5)|
|Unreported||519 (7.4)||313 (15.6)|
The role of race in predicting patient adherence has not been well established, and studies have shown conflicting data. The effect is most likely influenced by a number of factors, which limits the assumptions that can be made from the analysis. In our cohort, African American patients with PDR and nAMD had a significantly increased odds of LTFU (approximately 50%) when compared to whites. This is even after adjusting for other potential confounding factors. Asians with nAMD also demonstrated an increased odds of LTFU (160%) when compared to whites, however LTFU odds were similar when comparing Asians with PDR to whites with PDR. The Chinese eye study may help in the interpretation of this disparity. The study indicates that Chinese Americans over the age of 50 years have a high rate of nonadherence to eye-care follow-up. This is attributed to different factors such as language barriers and years living in the proximal region.6 Another interesting finding was the increased odds of LTFU in patients who refused to identify their race when compared to whites (~100% to 200%). This is particularly concerning given the size of the cohort. Previous studies have shown that patients with an unknown race receive fewer injections annually than whites.7 The reason behind these disparities remain are unclear, however this may be secondary to a psychosocial component that reflects a distrust in the health care system.
There was a similar trend of increased LTFU rates as regional adjusted gross income decreased. Rates ranged from 20% to 25% for incomes greater than $100,000 and rates of more than 30% for incomes less than $50,000 for both diseases. The role of regional adjusted gross income in determining patient health had been previously established by public health studies. Indeed, individuals from lower regional adjusted gross incomes have greater mortality rates.8 It is believed the regional environment may play a role in shaping the population’s attitude toward healthcare and its providers. This may serve as a powerful predictor that can direct future intervention to susceptible communities.
Interestingly, the role of visual acuity on LTFU varied by disease, with PDR patients demonstrating no significant variability in rates of LTFU by visual acuity at final injection and nAMD patients demonstrating a stepwise increased odds of LTFU as visual acuity worsened. This was somewhat anticipated given previous conflicting findings in studies evaluating patient adherence to follow-up.9-11 Although there is no concrete explanation, patients might be more encouraged to comply with treatment if the response to treatment is good. Interestingly, the patients most susceptible appear to be those who do not appreciate any change in visual acuity over time. These patients demonstrated a 50% increased odds of LTFU compared to patients who improved by 2 lines of vision. This is relevant as we expect a sizable portion of patients to maintain and not necessarily gain vision with sustained treatment. Therefore, future interventions that stress the importance of treatment on vision maintenance could help reduce LTFU after treatment.
Distance to Clinic
The distance patients had to travel to a clinic also appeared to be a variable that influenced LTFU rates depending on the disease. For patients with nAMD, LTFU odds significantly increased for distances greater than 20 miles. This was not observed in the PDR cohort. The more interesting finding is the distance distribution, with a majority of patients located within 20 miles of their respective clinic. Previous studies have demonstrated that a majority of patients live within approximately 20 minutes’ driving distance from ophthalmologist.12 This may suggest that distance plays more of a role in patients initiating care rather than continuing treatment.
Ongoing treatment and monitoring of nAMD and PDR is critical to prevent vision loss. Our studies have demonstrated that there is a sizable portion of patients (approximately 25%) that are LTFU after treatment. Moreover, our studies suggest that several demographic risk factors may contribute to LTFU. These results, however, are reflective of a single practice, and therefore they may not be generalizable to other populations. Therefore, it is imperative that future studies evaluate LTFU and potential risk factors across a variety of regions and populations. This will help establish specific and common risk factors that can help shape future patient care. RP
- Sloan FA, Yashkin AP, Chen Y. Gaps in receipt of regular eye examinations among medicare beneficiaries diagnosed with diabetes or chronic eye diseases. Ophthalmology. 2014;121(12):2452-2460.
- Sloan FA, Brown DS, Carlisle ES, Picone GA, Lee PP. Monitoring visual status: why patients do or do not comply with practice guidelines. Health Serv Res. 2004;39(5):1429-1448.
- Obeid A, Gao X, Ali FS, et al. Loss to follow-up in patients with proliferative diabetic retinopathy after panretinal photocoagulation or intravitreal anti-VEGF injections. Ophthalmology. 2018;125(9):1386-1392.
- Obeid A, Gao X, Ali FS, et al. Loss to follow-up among patients with neovascular age-related macular degeneration who received intravitreal anti–vascular endothelial growth factor injections. JAMA Ophthalmol. 2018;136:1251-1259.
- Gross JG, Glassman AR, Liu D, et al. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136(10):1138-1148.
- Jiang X, Varma R, Torres M, Hsu C, McKean-Cowdin R; Chinese American Eye Study Group. Self-reported use of eye care among adult Chinese Americans: the Chinese American eye study. Am J Ophthalmol. 2017;176:183-193.
- Curtis LH, Hammill BG, Qualls LG, et al. Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 medicare beneficiaries. Am J Ophthalmol. 2012;153(6):1116-1124.e1.
- Bosma H, Dike van de Mheen H, Borsboom GJJM, Mackenbach JP. Neighborhood socioeconomic status and all-cause mortality. Am J Epidemiol. 2001;153(4):363-371.
- Saadine JB, Fong DS, Yao J. Factors associated with follow-up eye examinations among persons with diabetes. Retina. 2008;28(2):195-200.
- Droege KM, Muether PS, Hermann MM, et al. Adherence to ranibizumab treatment for neovascular age-related macular degeneration in real life. Graefes Arch Clin Exp Ophthalmol. 2013;251(5):1281-1284.
- Boulanger-Scemama E, Querques G, About F, et al. Ranibizumab for exudative age-related macular degeneration: A five year study of adherence to follow-up in a real-life setting. J Fr Ophtalmol. 2015;38(7):620-627.
- Lee CS, Morris A, Van Gelder RN, Lee AY. Evaluating access to eye care in the contiguous united states by calculated driving time in the United States Medicare population. Ophthalmology. 2016;123(12):2456-2461.