Abstract
Purpose: To evaluate the visual, intraocular pressure (IOP), and anatomic outcomes of eyes with loss to follow-up (LTFU) after intravitreal or periocular steroid injections. Methods: Patients receiving intraocular or periocular steroid injections and with LTFU for at least 180 days were included in this retrospective cohort study. Charts were reviewed for the visual acuity (VA), IOP, and central foveal thickness at the visit before LTFU, the first return visit, and 3, 6, and 12 months after return. Results: Fifty-three eyes of 47 patients were identified. The mean (±SD) age was 62.3 ± 14.9 years, the mean LTFU time was 295 ± 181.2 days (range, 182-1101), and the mean follow-up after return was 354 ± 339.3 days (range, 32-1141). The overall mean number of steroid injections was 5.2 ± 3.9 (range, 1-18). Compared with the mean logMAR VA at the visit before LTFU (0.59 [Snellen 20/77]), the mean VA remained stable at all timepoints after return as follows: return visit (0.62 [20/83]; P = .6), month 3 (0.55 [20/70]; P = .6), month 6 (0.55 [20/70]; P = .5), month 12 (0.64 [20/87]; P = .6), and final visit (0.69 [20/97]; P = .2). At the first return visit, 8 (15%) of 53 patients had an IOP of 21 mm Hg or higher (range, 21-31); 2 required treatment with a new antihypertensive medication (latanoprost and timolol, respectively). Conclusions: Patients with LTFU after receiving steroid injections maintained their VA. No patient required incisional glaucoma surgery. Compared with other etiologies, eyes with diabetic macular edema had a greater increase in IOP.
Keywords: loss to follow-up, ocular steroid injections, macular edema, diabetes, uveitis
Introduction
Intravitreal and periocular injections of corticosteroids are among the most commonly performed procedures in ophthalmology. Intraocular or periocular administration provides high concentrations of medication while limiting systemic exposure. 1 Given that inflammatory pathways play an important role in the pathogenesis of disease, macular edema from diabetic retinopathy, venous occlusive disease, pseudophakic and aphakic macular edema (Irvine-Gass syndrome), and noninfectious uveitis remain the primary indications for corticosteroid injections. 2
Corticosteroids exert an anti-inflammatory effect that inhibits the arachidonic acid pathway, resulting in decreased leukotriene and prostaglandin synthesis. Corticosteroids also decrease other proinflammatory molecules, such as interleukin-6, intercellular adhesion molecule-1, and vascular endothelial growth factor (VEGF)-alpha, as well as increase vasoconstriction by inhibiting nitric oxide production.3,4 Moreover, corticosteroids reduce leukocyte recruitment and decrease blood–retinal barrier breakdown. 5
Several clinical trials have showed the safety and efficacy of intravitreal corticosteroids as first-line or second-line therapy in retinal vein occlusion (RVO), diabetic macular edema (DME), and noninfectious posterior uveitis.6,7 Long-acting intravitreal corticosteroid inserts and implants are commercially available, including Retisert (0.59 mg, fluocinolone acetonide, Bausch + Lomb/Valeant), Ozurdex (0.7 mg, dexamethasone, Allergan), Iluvien (0.19 mg, fluocinolone acetonide, Alimera Sciences, Inc), and Yutiq (0.18 mg, fluocinolone acetonide, EyePoint Pharmaceuticals, Inc). 8
Complications from intraocular and periocular steroid injections include those inherent to the injection itself as well as steroid-associated side effects, including cataract formation and increased intraocular pressure (IOP). 9 Previous studies found that steroids induce the myocilin gene in the trabecular meshwork and trigger the trabecular meshwork–inducible glucocorticoid response, which can lead to a subsequent increase in IOP.10–12 Increased IOP is more common in younger patients, after intravitreal injections than after sub-Tenon injections, and in eyes with a higher baseline IOP.9,13,14 As such, monitoring for potential IOP-related complications after a steroid injection is important because of the unique side-effect profile of these medications, especially the risk for glaucomatous optic neuropathy.
Our institution previously reported the outcomes of patients treated with intravitreal anti-VEGF injections for retinal diseases complicated by loss to follow-up (LTFU).15,16 However, little is known about the outcomes of eyes that have a nonintentional gap in evaluation after an intravitreal or periocular steroid injection, but this is important, in particular given the risk for possible IOP-related adverse events. This study evaluated the visual, IOP, and anatomic outcomes of patients who had intravitreal or periocular steroid treatment and resumed treatment after an LTFU period of 6 months or more.
Methods
This study was approved by the Wills Eye Hospital Institutional Review Board and was conducted in compliance with the US Health Insurance Portability and Accountability Act of 1996. The research adhered to the tenets of the Declaration of Helsinki. Patients receiving intraocular or periocular steroid injections of dexamethasone (Ozurdex), fluocinolone acetonide (Yutiq), or triamcinolone acetonide (Kenalog, Bristol-Myers Squibb; Triesence, Alcon Laboratories) were identified using the International Classification of Diseases 9th and 10th revisions and Current Procedural Terminology billing codes.
For inclusion, a period of LTFU was defined as no visits with an eye care provider for at least more than 180 days after an intravitreal or periocular steroid injection between January 1, 2015, and January 1, 2020. The patient was required to have at least 1 return visit after the period of LTFU for inclusion. Patients with more than 1 period of LTFU lasting more than 180 days were excluded from analysis.
Baseline characteristics, including age, sex, type of underlying retinal disease, lens status, number of steroid injections until LTFU, type of steroid medication, number of anti-VEGF injections until LTFU, history of glaucoma, neovascular glaucoma, ocular hypertension, and any prescription eyedrop use, were collected at the visit before LTFU. The best available Snellen visual acuity (VA) based on the better of pinhole testing or habitual correction, IOP, and various spectral-domain optical coherence tomography (OCT) parameters, including central foveal thickness (CFT), the presence or absence of intraretinal fluid (IRF) and subretinal fluid (SRF), and ellipsoid zone (EZ) disruption (qualitative observation of any EZ loss), were gathered at the visit immediately before LTFU. These same features were collected at the return visit; 3, 6, and 12 months after return; and at the final follow-up. The occurrence and type of new-onset ocular hypertension, including the addition of any IOP-related management, such as the initiation of topical antihypertensive drops, laser procedures, or incisional surgery, were also recorded.
All OCTs were obtained using a Spectralis HRA+OCT device (Heidelberg Engineering, Inc). CFT was defined from the inner border of the retina to the inner border of the hyperreflective layer of the retinal pigment epithelium and was measured manually using the caliper tool in Eye Explorer software (Heidelberg Engineering, Inc). All measurements were performed by the same investigator (R.M.). The Snellen VA was converted to logMAR notation for analysis.
All statistical analyses were performed using SPSS software (version 24, SPSS Inc). A generalized estimating equation that accounts for the intercorrelation between 2 eyes was used to compare the continuous and categorical variables longitudinally. The Pearson correlation coefficient was used to define the association between 2 continuous variables. For the final visual recovery analysis, the Fisher exact test was used for categorical variables while the independent t test and Mann-Whitney U test were used for continuous variables. Mean values are ± SD. Statistical significance was set at P < .05.
Results
Fifty-three eyes of 47 patients were eligible to be included in the final analysis. Table 1 shows the patients’ baseline characteristics. The mean age of the patients was 62.3 ± 14.9 years; 36 (67.9%) were women. The mean LTFU time was 295 ± 181.2 days (range, 182-1101), and the mean follow-up after return was 354 ± 339.3 days (range, 32-1141).
Table 1.
Clinical Characteristics of the Study Cohort at Baseline (N = 53 Eyes).
| Characteristic | Value |
|---|---|
| Mean age (y) ± SD | 62.3 ± 14.9 |
| Race, n (%) | |
| White | 30 (56.7) |
| Black | 21 (39.7) |
| Asian | 1 (1.8) |
| Other | 1 (1.8) |
| Sex, n (%) | |
| Male | 17 (32.1) |
| Female | 36 (67.9) |
| Reason for steroid injection, n (%) | |
| Uveitis-associated CME | 23 (43.5) |
| Diabetic macular edema | 13 (24.5) |
| Postsoperative CME | 13 (24.5) |
| Retinal vein occlusion | 4 (7.5) |
| Steroid type, n (%) | |
| Intravitreal | 22 (42) |
| Dexamethasone | 15 (28) |
| Triamcinolone acetonide | 7 (14) |
| Periocular triamcinolone | 31 (58) |
| Mean LTFU duration (d) ± SD | 295 ± 181.2 |
| Mean follow-up after return (d) ± SD | 354 ± 339.3 |
| Lens status, n (%) | |
| Phakic | 8 (15.1) |
| Pseudophakic | 45 (84.9) |
| Mean steroid injections (n) before LTFU ± SD | 3.4 ± 2.8 |
| Mean steroid injections (n) after return ± SD | 1.6 ± 2.4 |
| Mean anti-VEGF injections (n) before LTFU ± SD | 6.7 ± 3.2 |
| Mean anti-VEGF injections (n) after return ± SD | 3.8 ± 2.2 |
Abbreviations: anti-VEGF, antivascular endothelial growth factor; CME, cystoid macular edema; LTFU, loss to follow-up.
Table 1 also shows the indications for steroid injection, steroid type, lens status, and mean number of injections at LTFU and return. The most frequent indication for steroid injections was uveitis-associated cystoid macular edema (CME) followed by DME and postoperative CME; the least frequent was CME resulting from RVO. The most frequent injection preceding LTFU was an intravitreal steroid (dexamethasone or triamcinolone acetonide) followed by periocular triamcinolone. The overall mean number of steroid injections was 5.2 ± 3.9 (range, 1-18). The number of steroid injections before LTFU ranged from 1 to 18, and the number of additional steroid injections after returning until the final visit ranged from 0 to 10.
Visual Acuity
Table 2 shows the changes in VA over time across all eyes as well as by disease. In the overall cohort, the mean logMAR VA was 0.59 ± 0.51 (Snellen equivalent 20/77; n = 53) at the visit before LTFU and 0.62 ± 0.50 (Snellen equivalent 20/83; n = 53; P = .6) at the return visit. The mean logMAR VA 3 months after return was 0.55 ± 0.49 (Snellen equivalent 20/70; n = 35; P = .6), which remained stable 6 months after return (P = .6) but was slightly worse 12 months after the return visit (P = .6) and at the final visit (P = .2).
Table 2.
Mean LogMAR VA ± SD at Visit Before Loss to Follow-up Compared With Visits After Return. a
| Visit | ||||||
|---|---|---|---|---|---|---|
| Group | Baseline | Return | 3 Months After Return | 6 Months After Return | 12 Months After Return | Final |
| Full cohort | ||||||
| LogMAR | 0.59 ± 0.51 | 0.62 ± 0.50 | 0.55 ± 0.49 | 0.55 ± 0.37 | 0.64 ± 0.71 | 0.69 ± 0.60 |
| Snellen | 20/77 | 20/83 | 20/70 | 20/70 | 20/87 | 20/97 |
| Eyes (n) | 53 | 53 | 35 | 31 | 26 | 53 |
| P value b | — | .6 | .6 | .6 | .6 | .2 |
| Uveitis CME | ||||||
| LogMAR | 0.46 ± 0.43 | 0.52 ± 0.44 | 0.45 ± 0.38 | 0.50 ± 0.42 | 0.54 ± 0.75 | 0.59 ± 0.64 |
| Snellen | 20/57 | 20/66 | 20/56 | 20/63 | 20/69 | 20/77 |
| Eyes (n) | 23 | 23 | 16 | 14 | 12, P = .4 | 23, P = .2 |
| P value b | — | .4 | .4 | .6 | .4 | .2 |
| DME | ||||||
| LogMAR | 0.77 ± 0.52 | 0.72 ± 0.37 | 0.71 ± 0.28 | 0.78 ± 0.21 | 0.79 ± 0.40 | 0.75 ± 0.36 |
| Snellen | 20/117 | 20/105 | 20/102 | 20/120 | 20/123 | 20/112 |
| Eyes (n) | 13 | 13 | 8 | 6 | 6 | 13 |
| P value b | — | .6 | .4 | .6 | .6 | .9 |
| Postop CME | ||||||
| LogMAR | 0.54 ± 0.49 | 0.51 ± 0.48 | 0.64 ± 0.65 | 0.49 ± 0.38 | 0.51 ± 0.73 | 0.63 ± 0.62 |
| Snellen | 20/69 | 20/64 | 20/87 | 20/61 | 20/64 | 20/85 |
| Eyes (n) | 13 | 13 | 7 | 8 | 6 | 13 |
| P value b | — | .7 | .8 | .7 | .5 | .6 |
| RVO | ||||||
| LogMAR | 0.99 ± 0.80 | 1.2 ± 0.9 | 0.93 ± 0.92 | 0.89 ± 0.39 | 1.15 ± 0.93 | 1.25 ± 0.82 |
| Snellen | 20/195 | 20/317 | 20/170 | 20/155 | 20/282 | 20/355 |
| Eyes (n) | 4 | 4 | 3 | 3 | 3 | 4 |
| P value b | — | .2 | .4 | .7 | .3 | .2 |
Abbreviations: CME, cystoid macular edema; DME, diabetic macular edema; RVO, retinal vein occlusion; VA, visual acuity.
Visual acuity at each visit was compared with the visit before being lost to follow-up.
Change compared with baseline visit VA.
In the overall cohort, 17 eyes (32%) had worse VA at the return visit than at the visit before LTFU; the remaining 36 eyes (68%) had no significant change in VA. Of the 17 eyes with worse VA at the return visit, 10 (58.8%) lost 3 or more lines of VA. At the final visit, 25 eyes (47.1%) had worse VA than at the visit before LTFU; 11 (44%) of the 25 eyes lost 3 or more lines of VA. The only significant factor associated with visual recovery at the final visit was better VA at the return visit after LTFU. The mean VA was 0.33 ± 0.14 (Snellen equivalent 20/42) in eyes that recovered and 0.77 ± 0.57 (Snellen equivalent 20/117) in eyes without visual recovery (P = .04).
Intraocular Pressure
Table 3 shows the mean IOP at the visit before LTFU compared with the visits after return in the overall cohort and by disease. At the visit before LTFU, the mean IOP in the overall cohort was 13.9 ± 3.7 mm Hg (range, 8-22; n = 53). Compared with the visit before LTFU, there was no significant change in the mean IOP at the return visit (P = .2), 3 months after return (P = .2), 6 months after return (P = .7), 12 months after return (P = .2), or at the final follow-up visit (P = .1).
Table 3.
Mean IOP at Visit Before Loss to Follow-up Compared With Visits After Return.
| Visit | ||||||
|---|---|---|---|---|---|---|
| Group | Baseline | Return | 3 Months After Return | 6 Months After Return | 12 Months After Return | Final |
| Full cohort | ||||||
| IOP (mm Hg) | ||||||
| Mean ± SD | 13.9 ± 3.7 | 15.0 ± 4.9 | 15.1 ± 4.6 | 14.1 ± 3.2 | 15.2 ± 4.3 | 15.3 ± 4.5 |
| Range | 8, 22 | 8, 31 | 8, 30 | 8, 21 | 10, 30 | 8, 29 |
| Eyes (n) | 53 | 53 | 35 | 31 | 26 | 53 |
| P value a | — | .2 | .2 | .7 | .2 | .1 |
| Uveitis CME | ||||||
| IOP (mm Hg) | ||||||
| Mean ± SD | 13.5 ± 4.5 | 13.9 ± 4.7 | 15.0 ± 2.9 | 15.6 ± 2.8 | 13.4 ± 2.0 | 15.2 ± 4.9 |
| Range | 8, 22 | 10, 31 | 8, 18 | 12, 2 | 10, 16 | 8, 29 |
| Eyes (n) | 23 | 23 | 16 | 14 | 12 | 23 |
| P value a | — | .7 | .2 | .1 | .8 | .1 |
| DME | ||||||
| IOP (mm Hg) | ||||||
| Mean ± SD | 13.7 ± 2.7 | 17.4 ± 4.8 | 15.6 ± 4.6 | 14.5 ± 5.4 | 20.2 ± 6.8 | 16.4 ± 4.0 |
| Range | 10, 18 | 10, 25 | 10, 22 | 10, 21 | 15, 30 | 10, 23 |
| Eyes (n) | 13 | 13 | 8 | 6 | 6 | 13 |
| P value a | — | .04 | .3 | .7 | .02 | .06 |
| Postop CME | ||||||
| IOP (mm Hg) | ||||||
| Mean ± SD | 14.15 ± 3.2 | 15.3 ± 4.5 | 15.2 ± 8.1 | 12.8 ± 2.4 | 13.8 ± 2.6 | 14.0 ± 3.5 |
| Range | 10, 19 | 10, 22 | 10, 30 | 10, 16 | 10, 17 | 9, 22 |
| Eyes (n) | 13 | 13 | 7 | 8 | 6 | 13 |
| P value a | — | .3 | .5 | .2 | .7 | .4 |
| RVO | ||||||
| IOP (mm Hg) | ||||||
| Mean ± SD | 16.2 ± 2.7 | 14.0 ± 7.4 | 14.3 ± 1.2 | 14.3 ± 0.39 | 18.5 ± 3.5 | 16.1 ± 7.1 |
| Range | 13, 19] | 10, 25 | 13, 15 | 13, 15 | 16, 21 | 10, 26 |
| Eyes (n) | 4 | 4 | 3 | 3 | 3 | 4 |
| P value a | — | .4 | .1 | .1 | .2 | .9 |
Abbreviations: CME, cystoid macular edema; DME, diabetic macular edema; IOP, intraocular pressure; RVO, retinal vein occlusion.
Change compared with baseline visit VA.
At the visit before LTFU, 10 (19.6%) of 51 eyes required IOP-lowering eyedrops; of these, 6 had primary open-angle glaucoma and 4 had a history of ocular hypertension. The mean IOP in the 10 eyes using IOP-lowering drops was 16.5 ± 2.9 mm Hg (range, 10-17) at the visit before LTFU; the IOP remained stable at the first return visit after LTFU (mean, 14.4 ± 2.4 mm Hg; range, 12-15; P = .2). Of these 10 eyes, 4 had a history of tube-shunt surgery and 2 had a history of selective laser trabeculoplasty. All 4 eyes with a history of glaucoma surgery were using 1 or 2 eyedrops for IOP control (timolol, dorzolamide, or both), and the other 6 eyes were receiving topical drops only (3 timolol and dorzolamide; 3 travoprost and dorzolamide).
Overall, at the first return visit after LTFU, 8 (15%) of 53 eyes had an IOP of 21 mm Hg or higher (range, 21-31); none had a history of glaucoma diagnosis or IOP elevation from presentation at the retina clinic to the visit before LTFU. Of the 8 eyes with an IOP of 21 mm Hg or higher at the return visit, 3 (37.5%) had received a periocular triamcinolone injection at the visit before LTFU and 5 (62.5%) had received intravitreal dexamethasone. The type of steroid agent injected at the visit before LTFU had no significant impact on the chance of an IOP increase to above 21 mm Hg at the return visit (3/31 triamcinolone and 5/15 dexamethasone; P = .09, Fisher exact test). None of these eyes were on topical steroid drops before LTFU or after return from LTFU. Moreover, 4 of the 8 eyes had a history of anti-VEGF injection before LTFU; however, none had received anti-VEGF simultaneously with steroid injection at the visit before LTFU. The mean number of days for receiving anti-VEGF before LTFU was 78 ± 48 (range, 35-120).
Of the 8 eyes with an IOP greater than 21 mm Hg at the return visit, 2 (1 with a history of intravitreal dexamethasone and 1 with a history of periocular triamcinolone) required treatment with 1 new antihypertensive medication (latanoprost and timolol, respectively) at the return visit. The IOP in the other 6 eyes returned to normal 3 months later without intervention. No patient required laser treatment or incisional surgery.
The mean IOP in eyes using eyedrops before LTFU was 16.5 ± 2.9 mm Hg (range, 10-17) at the visit before LTFU; the IOP remained stable at the first return visit after LTFU (mean, 14.4 ± 2.4 mm Hg; range, 12-15; P = .2). None of these eyes had an increase in IOP at the later follow-up visits. The mean IOP at the final visit was 15.9 ± 2.9 mm Hg (range, 10-18; P = .6).
For 18 (33.9%) of 53 eyes, the steroid injection was their first. For 3 of the 8 eyes (37.5% that returned with elevated IOP), the injection was their first (P = .84). The mean number of steroid injections before LTFU was 4 (range, 1-10) in eyes that had elevated IOP on return, which was not significantly different from the number of previous steroid injections in eyes that returned with normal IOP (mean, 3.37; range, 1-13; P = .097).
Central Foveal Thickness
Table 4 shows the mean CFT at the visit before LTFU compared with visits after return in the overall cohort and by disease. In the overall cohort, the mean CFT was 369 ± 162 µm at the visit before LTFU (n = 53) and increased to 392 ± 240 µm at the return visit after LTFU (n = 53) (P = .35). Compared with the visit before LTFU, there was no significant difference in the mean CFT by 3 months after return (P = .8). In contrast, there was a significant decrease in the mean CFT 6 months after return (P = .005) and 12 months after return (P < .001). The mean CFT was slightly thinner at the final follow-up visit than at the visit before LTFU (P = .6).
Table 4.
Mean CFT at Visit Before Loss to Follow-up Compared With Visits After Return.
| Visit | ||||||
|---|---|---|---|---|---|---|
| Group | Baseline | Return | 3 Months After Return | 6 Months After Return | 12 Months After Return | Final |
| Full cohort | ||||||
| Mean CFT (µm) ± SD | 369 ± 162 | 392 ± 240 | 370 ± 222 | 294 ± 127 | 269 ± 112 | 352 ± 223 |
| Eyes (n) | 53 | 53 | 35 | 31 | 26 | 53 |
| P value a | — | .35 | .8 | .005 | <.001 | .6 |
| Uveitis CME | ||||||
| Mean CFT (µm) ± SD | 348 ± 178 | 389 ± 195 | 366 ± 267 | 227 ± 35 | 233 ± 69 | 367 ± 265 |
| Eyes (n) | 23 | 53 | 16 | 14 | 12 | 23 |
| P value a | — | .4 | .8 | .001 | .01 | .7 |
| DME | ||||||
| Mean CFT (µm) ± SD | 386 ± 208 | 421 ± 243 | 359 ± 167 | 272 ± 204 | 214 ± 162 | 445 ± 239 |
| Eyes (n) | 13 | 13 | 8 | 6 | 6 | 23 |
| P value a | — | .4 | .6 | .1 | .03 | .5 |
| Postop CME | ||||||
| Mean CFT (µm) ± SD | 384 ± 101 | 381 ± 103 | 329 ± 68 | 387 ± 114 | 339 ± 91 | 277 ± 140 |
| Eyes (n) | 13 | 13 | 7 | 8 | 6 | 13 |
| P value a | — | .8 | .2 | .9 | .1 | .02 |
| RVO | ||||||
| Mean CFT (µm) ± SD | 379 ± 88 | 362 ± 95 | 410 ± 110 | 330 ± 105 | 376 ± 85 | 316 ± 130 |
| Eyes (n) | 4 | 4 | 4 | 3 | 2 | 4 |
| P value a | — | .1 | .3 | .1 | .9 | .3 |
Abbreviations: CFT, central foveal thickness; CME, cystoid macular edema; DME, diabetic macular edema; RVO, retinal vein occlusion.
Change compared with baseline visit VA.
Intraretinal Fluid and Subretinal Fluid
IRF was present in 34 (64.1%) of 53 eyes at the visit before LTFU. The proportion of eyes with IRF increased to 71.6% (38/53 eyes) at the return visit (P = .3). Three months after return, the proportion of eyes with IRF decreased to 51.4% (18/35 eyes) compared with the visit before LTFU (P = .1). No significant difference was found in the proportion of eyes with IRF 6 months after return (41.5% [13/31 eyes]; P = .08). Twelve months after return, there was a significant decrease in the proportion of eyes with IRF (34.6% [9/26 eyes]; P = .002). There was an overall decrease in the proportion of eyes with IRF by the final follow-up visit (45.2% [24/53 eyes]; P = .07) compared with the visit before LTFU.
SRF was present in 10 (18.8%) of 53 eyes at the visit before LTFU. The proportion of eyes with SRF increased to 28.3% (15/53 eyes) at the return visit (P = .1). At the final follow-up, there was no significant difference in the proportion of eyes with SRF (15.1% [8/53]; P = .7) compared with the visit before LTFU.
Ellipsoid Zone Disruption
EZ disruption was found on OCT in 21 (39.6%) of 53 eyes at the visit before LTFU. The proportion of eyes with EZ disruption increased 47.1% (25/53 eyes) at the return visit (P = .5). At the final follow-up, there was no significant difference in the proportion of eyes with EZ disruption (33.9% [18/53 eyes]; P = .6) compared with the visit before LTFU.
There was also no significant correlation between the type of steroid injection used before LTFU and the change in VA or CFT from the visit before LTFU to the return visit (P = .4 and P = .8, respectively).
Conclusions
Our study evaluated the effect of LTFU on visual, IOP, and anatomic outcomes after intravitreal or periocular steroid injections. The mean VA decreased slightly at the return visit, and 10 (18.8%) of 53 eyes had lost 3 lines of VA by the time they returned. Moreover, 8 (15%) of 53 eyes had new-onset elevation in IOP of more than 21 mm Hg, with eyes with DME more likely to have an increase in IOP after return than eyes with other disease etiologies.
Anatomic characteristics, including CFT, the presence or absence of IRF or SRF, and EZ disruption, were not significantly different compared with the visit before LTFU. The frequency and impact of LTFU has been well documented for a range of conditions and treatments.15–18 In our study, significant morbidity was not observed in this population.
Many studies have discussed the timing of IOP increase or glaucoma in patients receiving systemic, topical, periocular, or intraocular corticosteroids.19–21 In a study by Reid et al, 22 the incidence of IOP increase was highest 2 months after placement of an intravitreal dexamethasone implant in eyes with macular edema secondary to RVO. In addition, the mean IOP returned to baseline after 6 months. This pattern also correlated with results in a randomized sham-controlled trial of intravitreal dexamethasone implants in patients with macular edema resulting from RVO. In the GENEVA study, 24 the maximum dexamethasone effect occurred 60 days after injection and returned to baseline by 6 months after injection. 23 The MEAD study, 24 a 3-year randomized sham-controlled trial of intravitreal dexamethasone implants in patients with DME, reported that the overall chance of an IOP increase after implant placement was mild and the peak IOP increase was at weeks 6 to 8; the IOP returned to normal at weeks 12 to 16. Given these previous data, the LTFU interval was selected at 6 months because after that, the IOP would generally be expected to return to baseline.
In our study, no patient required incisional glaucoma surgery for an increase in IOP after LTFU. These findings are consistent with the results in previous studies evaluating the need for incisional surgery after use of intravitreal or periocular steroids. A study by Capone et al 25 evaluated the safety and efficacy of repeated intravitreal dexamethasone implant injections in patients with RVO; only 1.7% of eyes required incisional glaucoma surgery. Results from the FAME study showed that 1.5% of eyes with an increase in IOP secondary to fluocinolone acetonide (FAc) implants needed incisional glaucoma surgery at 18 months of follow-up, while other studies, including the Intelligent Research in Sight (IRIS) Registry and Medisoft, showed that 0.8% of eyes required incisional glaucoma surgery during an 18-month follow-up.26–28 In a study by Iwao et al, 29 26 (22.5%) of 115 patients who received periocular triamcinolone injections for different underlying diseases ended up with IOP elevation to 24 mm Hg or higher; of these patients, only 1 (0.9%) required incisional glaucoma surgery within 12 months of follow-up. Sen et al 30 reported that 34% of eyes with uveitis had an IOP increase to 24 mm Hg or higher, and 2.4% required incisional glaucoma surgery. The higher rate of incisional glaucoma surgery in eyes with uveitis may reflect the effect of intraocular inflammation on IOP increases and less of a response to topical ocular antihypertensive medication. 30
A meta-analysis by Jonas 31 found that the proportion with an IOP increase of 21 mm Hg or more after intravitreal injection of triamcinolone acetonide was 41.2%; 99% were successfully treated with topical antiglaucoma drops. Studies of the efficacy and safety of FAc intravitreal implants found that the overall chance of IOP elevation was higher after FAc implants than after intravitreal triamcinolone acetonide. The possible mechanism is the longer lifespan of FAc implants compared with intravitreal triamcinolone acetonide implants. 32 However, the overall rate of eyes that required incisional glaucoma surgery was low. Most of the later studies showed that there is still a low chance of severe IOP elevation resulting in incisional glaucoma surgery in real-world studies compared with clinical trials of FAc implants.
This study has limitations. Because of its retrospective nature, the analysis was limited to the available data. The sample was relatively small, with heterogeneous diagnostic indications for steroid injections. Selection bias is also present because we were unable to analyze eyes that never returned after a steroid injection. As a result, the conclusions are applicable only to the population that did return. In addition, we are unable to draw conclusions about the effect of LTFU on patients who received the longer lasting FAc implants because no patient met the inclusion criteria. Finally, in this retina practice, routine OCT imaging of the nerve fiber layer and visual field is not performed.
In conclusion, the findings in this study show that patients managed with steroid medication with LTFU may continue to maintain stable vision and retinal anatomy despite suboptimal monitoring. Although a minority of patients (<20%) had a severe decrease in VA (3 or more lines) at the initial return after LTFU, as a cohort, patients maintained stable vision and tended to recover with ongoing care. Moreover, the reinitiation of treatment, even 6 months later, appears to have had a positive impact on long-term outcomes. Given the significant LTFU rates for chronic retinal diseases in the real-world setting, it is vital for the clinical team to make ongoing attempts to re-engage and reinstitute care for patients to optimize long-term vision and anatomic outcomes.
Footnotes
Authors’ Note: Presented at the American Society of Retina Specialists 2021 meeting and the Association for Research in Vision and Ophthalmology 2021 meeting.
Ethical Approval: This case report was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected patient health information were performed in a US Health Insurance Portability and Accountability Act–compliant manner.
Statement of Informed Consent: Written informed consent to publish potentially identifying information, including permission for all photographs and images included herein, was obtained from the patients.
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Garg is a consultant to Allergan and Bausch + Lomb.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
ORCID iDs: Raziyeh Mahmoudzadeh 
https://orcid.org/0000-0002-5818-9083
Varun Chaudhary
https://orcid.org/0000-0002-9988-4146
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