Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGRα), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside

Acute retinal pigment epithelium detachments after photocoagulation

To characterize the morphology of patterned scanning laser (PASCAL) panretinal photocoagulation. In this prospective cohort study, patients with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy with high-risk characteristics, who were treated with PASCAL panretinal photocoagulation as part of their indicated clinical course, were serially imaged with spectral domain optical coherence tomography. Thirty eyes of 25 patients were studied from 1 hour to 21 weeks after laser treatment. Over a quarter (26.1%) of all treatment spots were imaged by spectral domain optical coherence tomography 1 hour after PASCAL panretinal photocoagulation. At 1 hour (±30 minutes) after PASCAL treatment, spectral domain optical coherence tomography demonstrated retinal pigment epithelium detachment in 23 of 27 eyes (85.2%) and in 36.1% of all imaged laser spots. Detachments occurred preferentially at the photocoagulation edges in 48.4% of pigment epithelium detachments (PEDs). Linear regression analysis revealed that average laser power (Pearson's r = 0.671, P 1,200 mW. By a 1-week follow-up, no PEDs were observed, and the retinal pigment epithelium appeared morphologically similar to its preoperative structure by 3 weeks. Patient characteristics (study eye, sex, race, diagnosis, age, preoperative blood glucose, hemoglobin A1C, duration of diabetes, and body mass index) and other PASCAL parameters (number of laser applications, spot size, pulse duration, and average laser fluence) were not significantly associated with PEDs. Retinal pigment epithelium detachment occurs 1 hour after PASCAL treatment over a wide range of laser settings. Laser power and energy are positively correlated with the occurrence of PEDs, which are no longer observed by 1-week follow-up. Future studies might examine various acute posttreatment time points and directly compare the morphology of PASCAL burns with that of longer pulse-duration laser modalities

Prophylactic Scleral Buckle Implantation in Knobloch Syndrome

Knobloch syndrome is a rare autosomal recessive disorder characterized by a triad of high myopia, vitreoretinal degeneration, and congenital occipital scalp defects. On literature review of all reported cases, 25 of 85 eyes (29%) of patients diagnosed as having Knobloch syndrome have suffered retinal detachment. Due to high myopia, surgical repair of the retinal detachment is challenging and patients frequently require several reoperations. Even after vitrectomy or scleral buckle for retinal detachment, the final visual acuity outcomes are poor, with 11 of 12 (92%) patients having 20/ 200 visual acuity or worse and 6 of 12 (50%) having counting fingers visual acuity or worse. The role of retinal detachment prophylaxis has been discussed for other vitreoretinal degeneration disorders, but not for this disease. The authors report the case of a child affected with Knobloch syndrome who presented with total retinal detachment in the left eye at 24 months of age. He underwent successful repair and was then treated with prophylactic scleral buckle implantation in the right eye 5 months later. The retina in both of his eyes remains attached 4 years later

The tipping point: Tamoxifen toxicity, central serous chorioretinopathy, and the role of estrogen and its receptors

Purpose: To describe a case of tamoxifen toxicity superimposed on central serous chorioretinopathy (CSCR). We review the role of estrogen and the effect of tamoxifen on ocular tissues. Observations: A 32-year-old Hispanic female with infiltrating ductal carcinoma of the left breast (T2N1M0, triple-positive), status post chemotherapy and bilateral mastectomy, presented with complaint of a floater and decreased central vision of the right eye (OD). Symptoms began three weeks after initiating tamoxifen and five months after the last cycle of chemotherapy and dexamethasone. Visual acuity (VA) was 20/30 OD at presentation. Clinical examination and multimodal imaging revealed subretinal fluid (SRF) and pigment epithelial detachment (PED) suggestive of CSCR. After one month of monitoring, VA improved to 20/20; there was SRF resolution, small PED, and focal ellipsoid zone (EZ) band loss. Two weeks later, after undergoing surgery and starting a topical steroid, she returned with count fingers (CF) VA and large SRF OD. Steroid cessation improved SRF after one month, but VA was unchanged. Tamoxifen was discontinued, and VA improved to 20/100 with near-complete resolution of SRF at three weeks, and significant reduction in choroidal thickness at two months. At final follow-up, VA was 20/200, and there was focal EZ band loss sub-foveally, minimal SRF, and small PED. Conclusions and Importance: Treatment with tamoxifen may lead to ocular toxicity and can complicate the recovery course of patients affected with CSCR. Variations in levels of the estrogen receptor-alpha (ER-α) and treatment with tamoxifen (ER-α partial agonist) may lead to loss of the protective effect of estrogen in the retinal pigment epithelial cells in premenopausal women. Furthermore, tamoxifen toxicity can lead to focal photoreceptor loss. Treatment in these cases should be coordinated together with the oncologist

Visual and anatomical outcomes of macular epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair

To report outcomes and prognostic factors after epiretinal membrane peeling in patients with previous rhegmatogenous retinal detachment repair. A consecutive case series. Best-corrected visual acuity and optical coherence tomography characteristics were analyzed before and after epiretinal membrane surgery. Fifty-three eyes were analyzed. Best-corrected visual acuity improved by a mean of 10 letters at 1 month (N = 45; P = 0.001), 15 at 3 months (N = 42; P < 0.001), 11 at 6 months (N = 35; P = 0.001), and 16 at 12 months (N = 33; P < 0.001). The mean optical coherence tomography central foveal thickness decreased by 141 (N = 22; P < 0.001), 185 (N = 24; P < 0.001), 180 (N = 17; P = 0.001), and 151 μm (N = 9; P = 0.017) at 1, 3, 6, and 12 months, respectively. Better preoperative best-corrected visual acuity correlated with better best-corrected visual acuity at all follow-up visits (P ≤ 0.001). Intact preoperative inner segment/outer segment junction and external limiting membrane line, but not the change in central foveal thickness or location of fluid, correlated with better postoperative best-corrected visual acuity through 6 months. Epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair resulted in significant improvements in visual acuity and optical coherence tomography thickness, even in eyes with previous macula-involving rhegmatogenous retinal detachment. Better preoperative visual acuity and intact outer retinal layers by optical coherence tomography were the main prognostic factors for visual outcomes

Is it melanoma-associated retinopathy or drug toxicity? Bilateral cystoid macular edema posing a diagnostic and therapeutic dilemma

Purpose: To report the clinical presentation, multimodal imaging, and management of a patient with metastatic melanoma who presented with cystoid macular edema (CME). Observations: We report a case of a 71-year-old Caucasian male with metastatic melanoma who presented with bilateral cystoid macular edema after being on treatment with a programmed T cell death ligand 1 inhibitor, MPDL3280, for 1 year. Multimodal imaging techniques, including color fundus photographs, autofluorescence, spectral domain optical coherence tomography (OCT), fluorescein angiography (Spectralis, Heidelberg, Germany), and spectral-domain OCT angiography (Zeiss; California, USA) were performed to evaluate the etiology of his CME and to monitor his response to treatment. Clinical examination and multimodal imaging revealed 1 + chronic vitreous cells, an epiretinal membrane, and mild macular edema in both eyes. Fundus autofluorescence showed paravenous hypoautofluorescence in the right eye and scattered hypoautofluorescent spots in the left eye. Optical coherence tomography angiography (OCTA) revealed mild drop out of superficial vessels in the peri-foveal region bilaterally. These findings were concerning for melanoma-associated retinopathy, drug-related uveitis, or activation of a previous chronic autoimmune process. The patient was started on prednisone 30 mg oral daily and ketorolac tromethamine 0.5% 1 drop four times daily. He was then treated with bilateral sustained-release dexamethasone intravitreal implants (Ozurdex). He had complete resolution of CME, and was tapered off of oral steroids within 6 weeks. Conclusions and Importance: Melanoma-associated retinopathy can be accompanied by CME, which presents a diagnostic and therapeutic dilemma in cases where a new drug has been recently initiated. By treating the condition locally, the ophthalmologist may be able to taper systemic immunosuppression more quickly. Keywords: Cystoid macular edema, Melanoma, Melanoma-associated retinopathy, PD-L1 inhibitor, Optical coherence tomography angiography (OCTA), Multimodal imagin

Optic Nerve Aplasia, Chorioretinal Hypoplasia, and Microcornea After In Utero Infection With Cytomegalovirus

Optic nerve aplasia (ONA) is a rare phenomenon characterized by absence of the optic nerve, retinal blood vessels, and retinal ganglion cells. The authors report a case of optic nerve aplasia in association with congenital cytomegalovirus (CMV) infection, conveyed through multimodal imaging including color fundus photography, fluorescein angiography, and B-scan ultrasonography. Furthermore, the authors review the common ocular findings and previously reported cases of ONA in congenital CMV infection. Screening and counseling can be performed to advise parents about the potential risks and severity of this rare clinical manifestation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e171-e175.]