Foreign Body Reaction, Retinal Degeneration, and Epiretinal Membranes Associated With Intravitreal Administration of PLGA Rods.

Long-acting delivery platforms for intravitreal therapies are an active area of research in ophthalmic drug development. The aim of these platforms is to decrease the burden of intravitreal therapies for patients, by increasing the period between intravitreal injections. This brief communication describes the in-life, histologic and immunohistochemical findings associated with repeat-dose intravitreal administration of poly D, L sustained lactide-co-glycolide polymeric rods, an intravitreal depot, in the cynomolgus monkey (Macaca fascicularis). These nonclinical investigations illustrate a pattern of foreign body reaction around intravitreal depots at the temporal pars plana and demonstrated the histopathologic and immunohistologic features of retinal degeneration and epiretinal membrane formation in the inferior retina.

Comparative analysis of macular microstructure by spectral-domain optical coherence tomography before and after silicone oil removal.

PURPOSE: To document comparative analysis of macular microstructures before and after silicone oil (SO) removal via spectral-domain optical coherence tomography and to assess the retinal changes associated with visual outcome. METHODS: Forty-six eyes that underwent vitrectomy with SO tamponade were included. Ophthalmic examinations were performed before SO removal and at Months 1, 3, and 6 postoperatively including best-corrected visual acuity and spectral-domain optical coherence tomography. The macular microstructures identified by spectral-domain optical coherence tomography were compared before and after SO removal, and tomographic parameters related to visual outcome were analyzed. RESULTS: Under SO tamponade, spectral-domain optical coherence tomography demonstrated macular tomographic findings: epiretinal membrane in 12 eyes (26.1%), cystoid macular edema in 9 (19.6%), undulated inner retina in 8 (17.4%), and submacular fluid in 4 (8.7%). The mean duration of SO tamponade was significantly longer in eyes with macular changes (6.3 ± 4.6 months) than those without changes (5.2 ± 4.4 months) (P = 0.02). A total of 13 eyes had peeling of epiretinal membrane or internal limiting membrane combined with SO removal. After SO removal, most of microstructural changes were resolved. In the eyes with macular epiretinal membrane or cystoid macular edema, final best-corrected visual acuity was significantly improved compared with baseline (P = 0.017, 0.049), which paralleled the decrease of central foveal thickness. Restoration of photoreceptor layer and external limiting membrane was achieved in 2 (4.9%) and 5 eyes (12.5%), and those with continuous photoreceptor layer or external limiting membrane had the better final best-corrected visual acuity. CONCLUSION: Under SO tamponade, macular microstructural changes were identified by spectral-domain optical coherence tomography and were associated with duration of SO tamponade. Most of the microstructural changes were recovered after SO removal, if needed, combined with macular surgery. Anatomic resolution was accompanied by postoperative visual improvement.

Bilateral Drug-Induced Uveitis and Epiretinal Membrane during the Treatment of a Metastatic Cutaneous Melanoma.

Purpose: To report the case of a drug-induced uveitis during the treatment of a metastatic cutaneous melanoma.Case report: A 75-year-old female treated with Dabrafenib and Trametinib due to a cutaneous melanoma stage IV presented with blurriness in both eyes. The examination revealed bilateral intraocular signs of inflammation, and fundoscopy showed bilateral changes at the posterior pole, such as chorioretinal folds and Neurosensory Retinal Detachment (NRD). Due to a worsening of Visual Acuity (VA) and persistence of intraocular inflammation in spite of topical prednisolone acetate treatment, the therapy with Dabrafenib + Trametinib was interrupted, after having been administered for 4 months, and replaced by Nivolumab. Fundus abnormalities and intraocular inflammation improved, but VA remained low due to the presence of an epiretinal membrane in the right eye. Then, a decreasing course of prednisolone eye drops was introduced for one more month and finally interrupted without the cessation of Nivolumab.Conclusion: Drug-induced uveitis has been increasing in the last few years due to the development of new biological agents for treatment of different types of tumours. The management of these adverse events should be handled in collaboration with oncologists and ophthalmologists and must be individualised and based on the risk-benefit balance. A case report of an uveitis and subsequent development of an epiretinal membrane during the treatment with Dabrafenib, Trametinib and subsequent Nivolumab for a metastatic cutaneous melanoma is reported here, in order to note the importance of an adequate follow-up of patients treated with these drugs.

Topical prostaglandin analogues and development of epiretinal membrane. / Análogos de prostaglandinas y desarrollo de membrana epirretinal.

OBJECTIVES: To determine whether patients with glaucoma and epiretinal membrane (ERM) use a greater proportion of prostaglandin analogues (PA) than a control group of patients with glaucoma without ERM. METHOD: A retrospective study of cases and controls was conducted in order to determine whether patients with glaucoma and ERM used a greater proportion of PA than a control group of patients with glaucoma without ERM. The diagnosis of de ERM was made by clinical examination and optical coherence tomography. RESULTS: The mean age of the cases was 77 years (SD: 8.68; 95% CI: 74.3-79.4), compared to the controls with 63 years (SD: 16.6; 95% CI: 70.1-78.5). The cases included 50% (n=26) men and 50% women (n=26), whereas in the controls 25.4% (n=16) of the cases were men and 74.6% (n=47) women. PA treatment was used in 59.6% (n=31) and 60.3% (n=38) of the cases and controls, respectively. There was no statistically significant difference in PA use between the 2groups (P=.939). CONCLUSIONS: In this study, an association between the use of AP and the development of ERM could not be demonstrated.

Histopathology and ultrastructure of rabbit retina after intravitreous injection of perfluorohexyloctane (F6H8).

PURPOSE: To describe changes in rabbit retina after intravitreous injection of perfluorohexyloctane (F6H8). METHODS: Intravitreous injections of C3F8 were performed in the right eye of 48 male New Zealand albino rabbits. All 48 eyes were injected with C3F8. The animals were divided in three groups of 18 each. 18 eyes (6 in each group) were used as controls and 30 (10 in each group) were further injected with F6H8. Animals were sacrificed at days 15, 30, and 60 and the eyes processed for light and electron microscopy and immunohistochemistry. RESULTS: Vitreous tracts were observed behind the lens in all groups. Epiretinal and retrolental membranes developed in most of the treated eyes. Light microscopy showed retinal vacuolization in all eyes. No significant ultrastructural changes appeared in any of them. Macrophages were observed in the inner limiting membrane. CONCLUSIONS: Ultrastructural findings can be considered signs of good tolerance to F6H8, though the appearance of epiretinal membranes associated with the presence of macrophagic response suggests we should refrain from using F6H8 until results from clinical trials are available.

Clinicopathological correlation of epiretinal membranes and posterior lens opacification following perfluorohexyloctane tamponade.

BACKGROUND/AIMS: Epiretinal and retrolental proliferation may occur during prolonged use of the novel tamponade agent perfluorohexyloctane (F(6)H(8)). This study aims to determine whether there is any histological evidence that F(6)H(8) has a role in the formation of these membranes. METHODS: Eight epiretinal membranes and three opaque posterior lens capsules were excised from patients in whom F(6)H(8) had been used as a long term retinal tamponade agent. The membranes and capsules were examined employing light microscopic methods, including immunohistochemistry. RESULTS: The epiretinal membranes showed histological features typical of proliferative vitreoretinopathy (PVR) epiretinal membranes, but they also exhibited a dense macrophagic infiltration. In addition, three of the membranes contained multinucleated cells. Macrophages represented up to 30% of the cells present and appeared to contain large intracytoplasmic vacuoles. Similar cells were seen on the back of the posterior lens capsule in one specimen and all three capsules had posterior migration of lens epithelium. CONCLUSION: The pathological findings are not simply those of PVR. The macrophage infiltration suggests that there may be a biological reaction to F(6)H(8) which could reflect its surmised propensity to emulsify. Further investigations concerning the cellular response to this promising tamponade agent are warranted.

Intravitreal bevacizumab for retinal vein occlusion and early growth of epiretinal membrane: a possible secondary effect?

AIMS: To report the early development of epiretinal membranes (ERM) in eyes with retinal vein occlusions (RVO) treated with intravitreal bevacizumab and to describe possible mechanisms that may be involved in the growth and contraction of these lesions. METHODS: Retrospective and interventional study that included 25 eyes of 25 patients with RVO (16 eyes with central retinal vein occlusion and nine eyes with branch retinal vein occlusion). After an initial 2.5mg/0.1ml intravitreal bevacizumab injection all patients were followed-up every 6 weeks. Re-treatments were based on visual acuity and optical coherence tomography findings. Results Twenty-five eyes were treated with bevacizumab and followed for 8.3 (range 4.5-13.5) months. Four eyes developed an ERM within 6-7weeks after the administration of bevacizumab. ERM was not associated with further deterioration of visual acuity or metamorphopsia in these patients. A rebound of macular oedema was observed in one patient with ERM and in two other patients. No other side effects were observed. CONCLUSIONS: Intravitreal bevacizumab may be associated with an early growth of ERM in eyes with RVO, although a causative relationship cannot be established. Future randomised clinical trials are necessary to determine the efficacy and safety profile of this novel therapy.

Clinical findings on the use of long-term heavy tamponades (semifluorinated alkanes and their oligomers) in complicated retinal detachment surgery.

BACKGROUND: Heavy tamponades for pathologies in the lower part of the retina are a new development, and different tamponades have recently come into clinical use: semifluorinated alkanes (F(6)H(6), F(6)H(8)) and their oligomers (OL62HV). METHOD: Nine patients had been operated on using F(6)H(8) (n=5) and by OL62HV (n=4). In all cases the reasons for using the tamponades were complicated retinal detachments in the lower part. In three cases the use was primary and in six cases tamponades were used after reoperations. In all cases the endotamponade was removed within 6 weeks. Fluorescein angiography (FLA) was performed in the F(6)H(8) group. RESULTS: In the F(6)H(8)group dispersion developed in two of the three aphacic patients. In two out of five cases soft epiretinal membranes and cellular material could be found between the substance and the lower periphery. In two membranes examined by light microscopy, cystic cells and amorphous material could be found. In one case (PDRP, aphacic) cyclophotocoagulation had to be performed because of persistent elevated IOP. FLA was unremarkable. In the OL62HV group, severe recurrent PVR reaction occurred in the lower periphery (2/4) and unusual precipitates were observed (4/4). In one case, after a normal postoperative period (VA 0.05 after 5 days) an extensive cellular reaction on the complete surface of the tamponade occurred. After 5 weeks VA was no light perception. During removal of the oligomer unusual adherent cellular components were found on the surface of the retina. The retina appeared necrotic, showed constricted retinal vessels and there was optic atrophy. Histologically, fluffy epiretinal material and a lens capsule obtained from one eye filled with OL62HV resembled the appearance with F(6)H(8). CONCLUSION: Heavy endotamponades on the basis of semifluorinated alkanes can lead to an unusual biological reaction and need further investigation before clinical use.