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Pushing Boundaries in DME and PDR: Treat & Extend with Aflibercept 8 mg – A Clinical Case
Abstract
We present the case of a 62-year-old male patient with proliferative diabetic retinopathy (PDR) and centre-involving diabetic macular oedema (DME) in the left eye. The patient was treated with 8 mg of intravitreal Aflibercept using a treat-and-extend (T&E) protocol. The patient, who was naïve to prior ocular treatment, achieved anatomical and functional improvement following the loading phase and subsequent maintenance therapy. As of the present moment, the therapeutic range has been effectively extended to Q12, however, given the stability of the clinical picture in both morphological and functional terms, a subsequent extension of the therapeutic range to Q16 has been deemed appropriate, demonstrating the potential of high-dose Aflibercept in reducing the burden of treatment while maintaining disease control.
Case Presentation
A 62-year-old man presented with complaints of blurred vision, metamorphopsia, and intermittent floaters in both eyes. His medical history included type 2 diabetes mellitus (T2DM), with management of this condition through oral hypoglycemic agents, but with poor control at the time of presentation. Additional comorbidities included hypertension and hypercholesterolemia. The patient’s family medical history included a diagnosis of type 2 diabetes mellitus (T2DM) in the patient’s father.
On ophthalmic examination, best-corrected visual acuity (BCVA) was 40 letters on the ETDRS chart in both eyes. Intraocular pressure measured 16 mmHg in the right eye and 18 mmHg in the left eye. Fundus examination of the both eyes revealed signs of diabetic retinopathy, including scattered hemorrhages, microaneurysms and hard exudates.
In particular, the left eye showed a charateristic multimodal imaging pattern:
- Fundus autofluorescence (FA) (picture 1) revealed multiple hypoautofluorescent spots corresponding to microhemorrhages throughout the posterior pole with a central hyperautofluorescent spot localized at the fovea, suggesting foveal metabolic stress.
- Spectral-domain optical coherence tomography (SD-OCT) demonstrated the presence of intraretinal fluid, characterized by multiple cystoid spaces mainly in the inner nuclear and outer plexiform layers (picture 2). Additional findings included hyperreflective foci, hard exudates, and disorganization of the inner retinal layers (DRIL), all of which were consistent with the diagnosis of diabetic macular edema. The central subfield thickness (CST) was measured at 345 µm and best-corrected visual acuity (BCVA) was 40 letters on the ETDRS chart.
- Fluorescein angiography (picture 3- early phase; picture 4 – late phase) of the left eye showed in the late phase a classic “petaloid” pattern of hyperfluorescence in the macular region, indicative of cystoid macular oedema resulting from inner haematoretinal barrier damage.
Additionally, prominent epiretinal new vessels with active leakage was observed in the inferior- nasal periphery, associated with area of retinal ischemia, indicative of proliferative diabetic retinopathy.
These findings confirmed the diagnosis of PDR and, given the severity of the ocular anatomical and functional condition, supported the combined approach of panretinal photocoagulation in conjunction with anti-VEGF intravitreal therapy.
Therefore, the patient agreed to undergo treatment with a treat-and-extend regimen with intravitreal Aflibercept 8 mg in the left eye. The loading phase consisted of three monthly injections, initiated on September 27, 2024.
The second injection was administered four weeks later, on October 25, 2024, and the third on November 22, 2024, completing the loading phase.
Following completion of the panretinal photocoagulation and the loading phase of intravitreal Aflibercept 8 mg, multimodal imaging revealed significant anatomical and functional improvement.
OCT (picture 5) of the left eye demonstrated a restored foveal contour with complete resolution of intraretinal cystoid spaces and CST reduced to 227 µm. Hyperreflective foci and hard exudates previously noted at baseline had markedly regressed, and the disorganization of the retinal inner layers (DRIL) was no longer appreciable. The external limiting membrane (ELM) and ellipsoid zone appeared continuous and intact, consistent with retinal structural recovery. Functionally, visual acuity improved to 45 ETDRS letters.
Color fundus photography (picture 6) confirmed the panretinal distribution of laser photocoagulation scars, with visible scatter laser burns across the mid and far periphery. The central macula showed notable reduction of hard exudates.
The combined therapeutic approach yielded a favorable response, with resolution of macular edema and stabilization of proliferative changes. These findings supported the decision to proceed with interval extension in the ongoing treat-and-extend regimen.
On January 17, 2025 eight weeks after the last injection of the loading phase, the patient received the first maintenance injection. During this visit, we noted that the best-corrected visual acuity (BCVA) remained stable at 45 ETDRS letters and OCT revealed only sparse intraretinal cysts and residual hyperreflective foci, with intact ellipsoid and external limiting membranes (picture 7). CRT was found to be constant, measuring 229 µm.
Due to the maintained anatomical and visual stability, the injection interval was extended again, this time to 12 weeks.
At 12 weeks following the previous intravitreal injection, the patient returned for a scheduled follow-up on April 11, 2025, at which time the second maintenance dose of Aflibercept 8 mg was administered. Clinical assessment revealed a stable and favorable response, both anatomically and functionally. Best-corrected visual acuity (BCVA) had improved to 48 ETDRS letters, reflecting continued functional recovery.
OCT imaging (picture 8) demonstrated complete resolution of intraretinal and subretinal fluid, with restoration of the foveal contour and no evidence of cystoid changes. There was near-complete regression of previously observed hard exudates and hyperreflective foci. Additionally, the integrity of the ellipsoid zone and external limiting membrane was preserved, indicating sustained retinal structural improvement. CRT was stable at 241 µm.
Given the absence of fluid and the consistent visual acuity gain, the clinical team opted to extend the treatment interval to 16 weeks, with the next intravitreal injection scheduled for August 1, 2025, thus leading the patient to receive just over 3 injections per year. This decision was based on both anatomical quiescence and functional stability.
This case demonstrates the strong efficacy and durability of Aflibercept 8 mg in a treatment-naïve patient with proliferative diabetic retinopathy and diabetic macular oedema. The treat-and-extend regimen proved to be an effective strategy for the long-term management of DME, reducing the treatment burden for the patient in terms of both number of injections and hospital visits while maintaining remission of macular oedema.