We retrospectively studied 18 eyes from 14 consecutive patients (age 64–91 years; six women, eight men) with diabetes mellitus, treated with the intravitreal FAc implant for chronic DME. All patients provided signed informed consent and were observed between 12 June 2018 and 15 May 2020 at the Ophthalmology Department of Fondazione Policlinico Universitario A. Gemelli IRCCS of Rome, Italy. This retrospective study adhered to the tenets of the Declaration of Helsinki and was approved by the ethics committee of Fondazione Policlinico Universitario A. Gemelli IRCCS (11 November 2020, ID 3166).
Inclusion criteria were age 18 years or older, a clinical and instrumental diagnosis of chronic DME, pseudophakia, previous panretinal laser photocoagulation and/or intravitreal injections of anti-VEGF and/or dexamethasone, FAc intravitreal implantation between 12 June 2018 and 14 February 2020, according to the drug reimbursability indication in the country of study.
Exclusion criteria were refusal to sign the informed consent, uncontrolled elevation of intraocular pressure (IOP), and retinal or choroidal disease other than DR that could affect CMT, ERG, and/or BCVA.
The washout period, before FAc implantation, was at least 3 months, regardless of the intravitreal drug previously administered (anti-VEGF or sustained-release dexamethasone implant).
In all patients, no focal laser and/or panretinal laser photocoagulation was performed in the 6 months prior to FAc implantation.
Treatment and Follow-up
The FAc implant was injected by the same physician (AMM) and administered under topical anesthesia and accurate disinfection of conjunctival sac with 5% povidone-iodine. The FAc implant was injected in the inferotemporal quadrant, 3.5–4 mm posterior to the sclerocorneal limbus. Postoperative care included (in all patients) antibiotic (moxifloxacin eye drops) three times daily for 5 days.
All patients underwent a complete ophthalmologic examination at baseline including BCVA, IOP measurement, optical coherence tomography (OCT), and Ganzfeld cone-mediated electroretinograms (according to a published technique) [19,20,21]. At month 1–3 post injection, we acquired data from all the aforementioned testing procedures. In addition, we performed ocular ultrasound.
In 14 patients (14 out of 18 treated eyes), CMT and BCVA were also measured at months 4–8, 9–14 post injection of the FAc implant, in addition to those obtained at baseline and months 1–3. In seven patients (seven treated eyes), the ERGs were recorded at months 4–8 and 9–14 post-FAc implant injection, in addition to the recordings obtained at baseline and month 1–3. In 13 patients, ERG PhNR and b-wave were also recorded in the fellow untreated eyes, taken as control eyes. Ocular ultrasound has been performed only once, in seven eyes from seven patients, during the follow-up.
The main outcome was mean change in CMT at month 1–3. Secondary outcomes were changes in CMT and BCVA from baseline to month 4–8 and 9–14 and changes in BCVA as well as components of the cone electroretinogram (cone b-wave and PhNR) from baseline to month 1–3, 4–8, 9–14 and the incidence of adverse events.
For each patient, Ganzfeld cone-mediated electroretinograms (Retimax, CSO, Firenze, Italy) were recorded with a specific, published protocol (employed to isolate and analyze the PhNR from the single flash cone-mediated responses) [19,20,21]. Typical ERG recordings are shown elsewhere . The amplitude of the PhNR and that of the cone b-wave were measured in each recording session. One of the 14 patients was not included in ERG measures analysis owing to his lack of cooperation during testing. For the purposes of the current study, we used normative values collected in age-matched control subjects as reference. The mean normal PhNR amplitude was 8 ± 2 µV; the mean normal b-wave amplitude was 22 ± 3 µV.
All the OCT acquisitions were performed using either an SD-OCT or an SS-OCT: the SD-OCTs were acquired either using a Spectralis OCT (Heidelberg Engineering, Inc.) or a Cirrus HD-OCT (Carl Zeiss, AG.); the SS-OCTs were acquired using a DRI OCT Triton (Topcon, Inc., USA). Each eye was analyzed by the same machine at baseline and during the follow-up period.
BCVAs were determined using ETDRS charts and were expressed as number of letters read.
Tonometry was performed with a Reichert non-contact tonometer (NCT) and confirmed with a Goldmann applanation tonometer (if IOP > 21 mmHg).
B-scan ocular ultrasonography was performed, in seven eyes from seven patients, by using the Optikon Hi Scan (software Optikon 2000, Optikon Rome, Italy) system according to a standardized method. Transpalpebral B-scans of the retina and vitreous body were acquired by orienting the 20-MHz probe at different meridians. B-scans were performed at month 1–3 after intravitreal FAc implant injection in order to define the position and kinetics of the implant.
All the previous mentioned instruments were regularly inspected and maintained by specialized personnel.
Data Registration and Acquisition
Data were extracted from the patients’ medical charts (either electronic or paper ones) and from their IDs in the electroretinographic machine, OCTs, and ultrasound equipment proprietary software.
Data were analyzed by non-parametric Wilcoxon test and Friedman’s non-parametric analysis of variance (ANOVA), comparing the measures obtained at follow-up with those recorded at baseline. Given multiple comparisons, a conservative p value less than 0.05 was considered to represent statistical significance.