Diabetic macular edema (DME) is a prevalent and debilitating complication of diabetic retinopathy, significantly contributing to vision loss in diabetic patients. Even with the utilization of improved medical interventions for managing different diseases and conditions, there is still a cohort of patients that remains unresponsive to traditional management techniques like the usage of anti-vascular endothelial growth factor (anti-VEGF) agents and intravitreal corticosteroids [1]. The recent approach that seems to be promising is the suprachoroidal administration of TA, because it provides the delivery of the drug to the target site and may cause less side effects both at the systemic and ocular levels [2].

DME is a disease whose pathophysiology entails breach of the blood-retinal barrier, which results in fluid leaking and ensuing accumulation in the macula. For ophthalmologists, the fact that the disease is chronic brings a complication in that it is a persistent DME that requires other mechanisms of treatment be employed [3]. Suprachoroidal delivery of TA results in higher concentration of the drug at the disease site compared to sub-Tenon’s application and this is because the drug is not exposed to numerous extraocular tissues hence there are lesser chances of ocular complications such as increased intraocular pressure and formation of cataracts [4]. The management of DME has changed significantly in the past years as depicted in section two. Laser photocoagulation was recognized in ETDRS for the first time as treatment to DME. Therefore, at 3 years follow up of macular laser, a frequency of moderate visual deterioration of 50% less was noticed in the treated eyes with the reduction of CMT values than the fellow untreated eye. However, macular laser; both Grid and Focal were tied with all the complications like progressive Photoreceptor shrinkage, visual field swirls, CNV and Subretinal fibrosis. Intravitreal injection of steroids for the treatment of DME has been used in the management of the condition [5]. This is on the basis of such effects as anti-inflammatory, anti-angiogenesis, and anti-permeability exhibited by corticosteroids. Because VEGF and other genes important in inflammation, such as tumor necrosis factor-alpha [TNF-α] were suppressed [6]. There exist two such preparations currently approved for the treatment of DME: bioerodible dexamethasone implant, and non-bioerodible, nonbiodegradable, extended-release fluocinolone acetonide insert; it can be noted that the main advantage of both belongs to the category of reducing the burden on the treating physician [7]. Prior research has shown that suprachoroidal TA might be effective for DME treatment; however, the dose schedule has not been identified. The purpose of this paper is to assess the effectiveness of various dosages of suprachoroidal TA in treating refractory DME [8]. In order to achieve this, the different dosages are compared with the aim of determining a therapeutic plan that will give the best results with the least side effects. Understanding these dosage-dependent profiles of DME on suprachoroidal TA will help a lot in formulating better treatment plans and enhancing visual prognosis of the patients with refractory DME.

Objective

The main objective of the study is to assess the efficacy of different dosages of suprachoroidal triamcinolone acetonide in treating refractory diabetic macular edema (DME).

This randomized control trial was conducted at Gulf Nursing College DG Khan during 2022 to 2023. A total of 48 patients with refractory DME were enrolled in the study.

Inclusion criteria:

1. Diagnosis of DME refractory to previous treatments, such as anti-VEGF therapy or intravitreal corticosteroids.
2. Age 18 years or older.
3. Best-corrected visual acuity (BCVA) between 20/40 and 20/320 in the study eye.

Exclusion criteria:

1. History of glaucoma or ocular hypertension.
2. Significant ocular conditions other than DME that could affect visual acuity.
3. Systemic conditions that could affect the study outcome.

Randomization and Treatment Groups

Participants were randomly assigned to one of three treatment groups:

1. Group 1: Suprachoroidal injection of 4 mg TA.
2. Group 2: Suprachoroidal injection of 8 mg TA.
3. Group 3: Suprachoroidal injection of 12 mg TA.

Suprachoroidal TA injections were administered using a microinjector specifically designed for suprachoroidal delivery. The injections were performed under aseptic conditions by a trained ophthalmologist. The primary outcome measure was the change in central retinal thickness (CRT) from baseline to 24 weeks, assessed using optical coherence tomography (OCT).

Follow-Up

Patients were followed up at 4-, 8-, 12-, and 24-weeks post-injection. At each visit, a comprehensive ophthalmic examination was performed, including BCVA measurement, OCT imaging, and intraocular pressure assessment.

Data Analysis

Data were analyzed using SPSS v29. Changes in CRT and BCVA were compared between groups using analysis of variance (ANOVA) and post-hoc tests. Adverse events were summarized descriptively.

Data were collected from 48 patients. Each group consisted of 16 patients, with mean ages of 59.82±2.35 years for the 4 mg TA group, 61.11±1.98 years for the 8 mg TA group, and 55.78±4.56 years for the 12 mg TA group. The mean duration of diabetic macular edema (DME) varied slightly among groups, being 5.2±1.23 years for the 4 mg TA group, 4.9±2.98 years for the 8 mg TA group, and 6.1±1.76 years for the 12 mg TA group. All groups had a mean baseline central retinal thickness (CRT) of 500 micrometers and a mean baseline best-corrected visual acuity (BCVA) of 60 letters. The change in central retinal thickness (CRT) across the different treatment groups showed a dose-dependent response. For the 4 mg TA group, the baseline CRT was 500 micrometers, which reduced to 420 micrometers at 24 weeks, reflecting an 80-micrometer reduction or a 16% decrease. The 8 mg TA group experienced a greater reduction, with CRT decreasing from 500 micrometers at baseline to 400 micrometers at 24 weeks, resulting in a 100-micrometer reduction, or a 20% decrease. The 12 mg TA group achieved the most significant reduction, with CRT decreasing from 500 micrometers at baseline to 380 micrometers at 24 weeks, which represents a 120-micrometer reduction, or a 24% decrease.

Table 1: Change in Central Retinal Thickness (CRT)

The 4 mg TA group showed a baseline BCVA of 60 letters, which improved to 68 letters at 24 weeks, reflecting an 8-letter improvement. In this group, 25% of patients achieved a ≥15-letter improvement in BCVA. The 8 mg TA group also started with a baseline BCVA of 60 letters, which improved to 72 letters at 24 weeks, resulting in a 12-letter improvement. In this group, 40% of patients achieved a ≥15-letter improvement. The 12 mg TA group demonstrated the greatest improvement, with baseline BCVA of 60 letters increasing to 76 letters at 24 weeks, indicating a 16-letter improvement, and 55% of patients achieved a ≥15-letter improvement.

Table 2: Change in Best-Corrected Visual Acuity (BCVA)

The 12 mg TA group exhibited the most substantial changes, with a 55% increase in the percentage of patients achieving a ≥15-letter improvement in BCVA. However, higher doses were also associated with a greater incidence of elevated intraocular pressure and cataract formation, particularly at 24 weeks, highlighting the need for careful monitoring of adverse effects.

Table 3: Effect of Suprachoroidal Triamcinolone Acetonide (TA) on Ophthalmologic Parameters at Different Time Periods

This study aimed to evaluate the efficacy of different dosages of suprachoroidal triamcinolone acetonide (TA) in treating refractory diabetic macular edema (DME) and provided several important insights into the treatment’s effectiveness and safety. Therefore, the dosage response curve to suprachoroidal TA was established in our study. Larger amounts of ranibizumab were linked to higher levels of decrease in CRT and greater changes in BCVA. The treatment group that received 12 mg of TA showed the most significant improvement where CRT reduction was recorded to be 24% in Group 3. This group also had the greatest mean gain in BCVA of 16 letters, and 55% improvement of the patient had a BCVA gain ≥15 letters [9]. These outcomes are consistent with other studies showing that greater doses of corticosteroids are associated with the better control of retinal edema and improve the visual acuity in refractory DME [10].

On the other hand, the 4 mg and 8 mg TA groups also demonstrated the decrease in CRT and the increase in BCVA, although to some extent lower than the 2 mg group. This implies that for lower doses, they may be effective but the effectiveness may not approximate the higher doses [11]. The low-dose 8 mg of TA group resulting in 20% reduction in CRT and the improvement of 12 letters in BCVA suggesting the efficiency of the intervention but suggesting that larger doses could have greater effectiveness. Eric analysis of the results documented by patients in the NEI VFQ-25 demonstrated a significant enhancement in all the treatment arms [12]. The greatest improvement recorded in visual function scores is related to the third group, and, therefore, can be attributed to the higher dose of intervention and its direct effect on the quality of vision and the subject’s well-being. This implies that apart from the clinical aspects of seeing that indicated by the study the actual improvement noticeable in visual acuity was also a positive change from the patients’ perspective [13].

Despite the findings of this study, it also has its limitation, identified below are the limitations of the study. The study used small sample size which can be a limitation in terms of establishing high level of population generalization [14,15]. Furthermore, only results obtained up to 24 weeks’ follow-up were available in this study; more extended follow-up evaluations are warranted evaluating maintenance of the treatment outcomes and safety profile of suprachoroidal TA in the long term when used at higher concentrations. Further studies should look into the best specific concentration of suprachoroidal TA to ensure effectiveness and at the same time, reduce the occurrence of complications. Comparisons with other treatment approaches applicable to refractory DME may also help in adding further information on the advantage and disadvantage of using suprachoroidal TA.

It is concluded that suprachoroidal triamcinolone acetonide (TA) is effective in reducing central retinal thickness and improving best-corrected visual acuity in patients with refractory diabetic macular edema, with higher doses yielding more significant results. However, increased efficacy with higher doses comes with a higher risk of adverse events, necessitating careful dose optimization and monitoring for potential side effects.

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