Subthreshold grid laser versus intravitreal bevacizumab as second-line therapy for macular edema in branch retinal vein occlusion recurring after conventional grid laser treatment.

PURPOSE: To compare the effects of subthreshold grid laser treatment (SGLT) and intravitreal bevacizumab injection (IVBI) for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) recurring after conventional grid laser photocoagulation. METHODS: Thirty-five eyes were considered in this prospective, randomised, interventional study and treated with micropulse diode laser (SGLT subgroup) or IVBI (IVBI subgroup). SGLT was administered once, whereas IVBI (1.25 mg) was given at baseline and then on a pro re nata regimen according to ME presence on optical coherence tomography (OCT), performed at monthly examinations over a 12-month follow-up. Primary outcome measures were the mean BCVA changes over the follow-up and the decrease in mean central foveal thickness (CFT) on optical coherence tomography (OCT). Secondary outcomes included the proportion of eyes that gained at least 15 letters (approximately three lines) at the 12-month examination. RESULTS: Eighteen and 17 patients were assigned to SGLT and IVBI subgroups, respectively. At baseline, the subgroups were similar with regard to mean ME duration, BCVA, and CFT. At month 12, mean CFT significantly improved from 484 µm to 271 µm in the IVBI subgroup, whereas it was unchanged in the SGLT subgroup. Mean BCVA changed from 0.92 ± 0.3 (LogMAR) to 0.99 ± 0.2 in the SGLT subgroup; in the IVBI subgroup, mean BCVA showed a statistically significant improvement from 0.94 ± 0.3 to 0.72 ± 0.2. Ten patients in the IVBI subgroup (58 %) and no patient in the SGLT subgroup gained at least three lines. CONCLUSION: At the 1-year follow-up, IVBI provided a significant functional and anatomical improvement, whereas SGLT failed to demonstrate any beneficial effects. IVBI might be a useful approach in the treatment of recurrent ME secondary to BRVO already treated with conventional grid laser photocoagulation. UMIN registry, number UMIN000005014, URL: http://www.umin.ac.jp/ctr/index.htm.

Pharmacological approach to diabetic macular edema.

Diabetic macular edema (DME) is a highly prevalent cause of vision loss and has a remarkable impact on public health, and on the quality of life of diabetic patients. Even though laser photocoagulation has been the standard of care for decades, a substantial group of patients are unresponsive and fail to improve after laser treatment. Recently, new pharmacological approaches based on the use of intravitreal drugs, such as corticosteroids and anti-vascular endothelial growth factor, have revolutionized the treatment of DME. The use of intravitreal drugs is supported by the improvement in visual acuity reported by several clinical trials and can limit the potentially destructive effects of the laser treatment. Encouraging results also emerged from studies evaluating the use of a combination therapy, or the association of intravitreal drugs and laser treatment. This review aims at providing a brief synopsis of the main investigations regarding the current pharmacological approach to DME.

Dexamethasone intravitreal implant: an effective adjunctive treatment for recalcitrant noninfectious uveitis.

PURPOSE: To describe our experience in treating recalcitrant and severe cases of noninfectious posterior uveitis with the 0.7-mg dexamethasone intravitreal implant as adjunctive anti-inflammatory treatment. PROCEDURES: Retrospective study. Twelve patients (8 females; 4 males; 14 affected eyes, 15 implants) with severe recalcitrant uveitis were treated. Patients had an inadequate control of uveitis despite different immunosuppressants and periocular corticosteroid therapy. Primary outcome measures evaluated were: decrease in uveitis activity, improvement in visual acuity, reduction of macular thickness, and occurrence of adverse events. RESULTS: Uveitis activity decreased in all patients after the implant. The mean follow-up time from injection was 9 months. Best-corrected visual acuity improved from 20/80 to 20/40 at the end of follow-up. The mean retinal thickness improved from 496 to 226 µm. Adverse events encountered were: 3 eyes with intraocular pressure elevation, 1 vitreous hemorrhage and 1 subconjunctival hemorrhage. Three patients reduced the daily systemic corticosteroid dosage after treatment. CONCLUSIONS: The 0.7-mg dexamethasone intravitreal implant appears to be a novel and promising adjunctive treatment for patients with severe posterior noninfectious uveitis recalcitrant to different immunosuppressive agents.

Evidence for anti-VEGF treatment of diabetic macular edema.

Diabetic macular edema (DME) is the most important cause of vision loss in patients with diabetes mellitus. Diabetic retinopathy has a remarkable impact on public health and on the quality of life of diabetic patients and thus requires special consideration. The first line of treatment remains the management of systemic risk factors but is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new strategies in the treatment of DME have been studied, in particular the use of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that acts as a vasopermeability factor and an endothelial cell mitogen. For this reason, it represents an interesting candidate as a therapeutic target for the treatment of DME. The aim of this article is to review the evidence behind the use of anti-VEGF drugs in the treatment of DME.

Pyogenic granuloma after cosmetic eye whitening. / Granuloma piogénico tras blanqueamiento ocular cosmético.

CLINICAL CASE: A 46-year-old caucasian male with a history of chronic conjunctival hyperemia, presented at our clinic 5 years after he underwent the surgical procedure of cosmetic eye whitening. On examination we observed pyogenic granuloma in the right eye; besides acute nongranulomatous anterior uveitis and necrotizing scleritis in both eyes. RESULT: Complete clinical evaluation and full work-up exclusion of systemic diseases was done. The pyogenic granuloma was treated with surgical resection, as well as anterior uveitis and necrotizing scleritis were successfully treated with systemic corticoesteroids and methotrexate. CONCLUSION: The surgical cosmetic eye whitening could have as complication the pyogenic granuloma in addition to necrotizing scleritis and nongranulomatous anterior uveitis; and be present 5 years after the procedure. The surgical resection is a successful treatment for this presentation of pyogenic granuloma.

Steroids as part of combination treatment: the future for the management of macular edema?

Diabetic macular edema (DME), defined as a retinal thickening involving or approaching the center of the macula, plays a major role in vision loss related to diabetic retinopathy. This article presents an in-depth analysis of therapeutic perspectives on DME by means of an approach based on combination therapy with steroids. Corticosteroid drugs have been demonstrated to both inhibit the expression of vascular endothelial growth factor (VEGF) and the VEGF gene, and to have antiinflammatory properties. A treatment algorithm is provided regarding the management of DME. While grid laser photocoagulation remains the first-line therapy for focal vasogenic DME, diffuse DME can be effectively treated by means of intravitreal injections of corticosteroids. Recalcitrant DME can also be managed beneficially with intravitreal steroids. The management of DME is complex, and often multiple treatment approaches are needed. Each form of DME should be properly classified and specifically treated. The combination treatment has still an important role in the combined treatment options for DME.

Nonvisible subthreshold micropulse diode laser (810 nm) treatment of central serous chorioretinopathy. A pilot study.

PURPOSE: To verify the efficacy of nonvisible micropulse diode laser irradiation in the treatment of central serous chorioretinopathy (CSC). METHODS: Twenty-two patients with CSC for a total of 24 eyes with a disease duration longer than 3 months were included in a prospective study. Patients underwent Early Treatment Diabetic Retinopathy Study visual acuity (VA) examination, dilated ophthalmoscopy, fluorescein angiography, and optical coherence tomography before treatment and during follow- up. Treatment with a micropulse diode laser was given with a duty cycle of 15%. Multiple spots were placed over and adjacent to the area of retinal pigment epithelium leak or decompensation. RESULTS: Mean follow-up was 14 months (range 3-36 months). Powers used ranged from 1 to 2 W (mean 1.35 W). Mean number of spots was 215 (range 90-400). Fourteen eyes were treated once, nine eyes received two to three treatments, and one eye had five treatments during a follow-up of 3 years. Subretinal fluid was resolved or improved in two third of cases 1 month after laser treatment, and in three-quarters at the end of follow-up. Mean retinal thickness was 328 microm, 197 microm, and 168 microm before, 1 month after irradiation, and at the end of follow-up, respectively. No evidence of RPE or retinal changes due to laser treatment were discernible in most of the eyes. Median VA was 20/32 (range 20/100-20/20) before treatment and 20/25 (range 20/200-20/20) at the end of the follow-up. CONCLUSIONS: Nonvisible micropulse diode laser may have efficacy in the treatment of CSC. A randomized study with larger series is needed.

Response of central serous chorioretinopathy evaluated by multimodal retinal imaging.

PurposeTo identify predictive biomarkers of treatment outcomes by multimodal retinal imaging in patients affected by central serous chorioretinopathy (CSC).Patients and methodsIn this interventional non-randomized clinical study, 27 treatment-naive CSC patients were prospectively enrolled and treated with oral eplerenone for 5-13 weeks. Primary outcomes included presence of pathological findings on indocyaine green angiography (ICGA), structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) at baseline associated with different response to the treatment.ResultsA total of 29 eyes of 27 patients (2 females, 25 males) met the inclusion criteria and were included in the study (mean age was 45±7 years). Mean CSC duration at baseline was 13.5±4.4 weeks. After a mean of 10.5 weeks of treatment, mean central macular thickness significantly reduced (P<0.001), and mean best-corrected visual acuity improved (P<0.001). Seventeen eyes (61%) demonstrated total reabsorption of subretinal fluid on structural OCT, five eyes (18%) presented a partial response to eplerenone therapy and six eyes (21%) showed no response. The complete response to the treatment was associated with absence of CNV at OCT-A and the presence of hotspot at ICGA (P<0.001 and P=0.002, respectively). None of eight eyes with CNV in OCT-A imaging had a complete response to eplerenone and none of three eyes without hotspot at ICGA showed a complete response to the treatment.ConclusionsMultimodal retinal imaging allowed us to propose predictive biomarkers (ie, absence of CNV on OCT-A and presence of hotspot on ICGA) for treatment outcomes.

Multimodal retinal imaging in central serous chorioretinopathy treated with oral eplerenone or photodynamic therapy.

PurposeTo correlate function and structural optical coherence tomography (OCT) to optical coherence tomography angiography (OCT-A) measures in patients affected by central serous chorioretinopathy (CSC) and to describe their changes after treatments (ie oral eplerenone, half-fluence photodynamic therapy (PDT)).Patients and methodsTwenty eyes of 16 consecutive patients with treatment-naïve CSC undergoing either eplerenone or PDT were enrolled in this prospective, observational study. All patients underwent structural OCT and OCT-A at baseline and after therapy at months 1 and 3.ResultsEleven eyes of nine patients and nine eyes of seven patients underwent eplerenone or PDT treatment, respectively. Central macular thickness (CMT) and subretinal fluid (SRF) correlated to fovea avascular zone (FAZ) area (r=0.74 and r=0.71, P=0.01) and vessel density (r=0.77 and r=0.68, P=0.01) at deep capillary plexus (DCP). CMT (P=0.0011), SRF (P=0.0005), SFCT (P=0.0016), FAZ area at DCP (P=0.0334) improved at 3-month visit. A significant reduction of deep FAZ area was appreciated in eplerenone (P=0.0204) but not in PDT (P=0.5) group. SFCT reduction was significantly higher in PDT than eplerenone group (P=0.0347).ConclusionStructural and vascular parameters are correlated in CSC and they improve after different treatments. Both half-fluence PDT and oral eplerenone do not permanently damage choriocapillaris or other choroidal layers as evaluated by OCT-A.

Choroidal excavation in choroidal osteoma complicated by choroidal neovascularization.

PurposeTo describe multimodal imaging features of choroidal osteoma (CO) complicated by choroidal neovascularization (CNV) and focal choroidal excavation (FCE).MethodsPatients presenting with CO and CNV between January and October 2016 were considered for this study. Diagnosis of CO was confirmed by ultrasound examination. All patients underwent multimodal imaging including optical coherence tomography (OCT), swept-source OCT angiography (DRI OCT Triton, Topcon, Inc., Tokyo, Japan) and fluorescein angiography (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany).ResultsTwo patients (one with bilateral CO) were included in the study. OCT showed a FCE in two eyes of two patients (one in correspondence of the CNV and the other adjacent to the CNV). OCT-A demonstrated presence of microvascular flow within neovascular network of the CNVs. Decalcification of the tumor was noted in correspondence of one eye with FCE.ConclusionsFCE may be found in eyes with choroidal osteoma and CNV. OCT-A was a valuable tool for detection of CNV complicating choroidal osteoma. Decalcification of choroidal osteoma may represent a common pathogenic pathway for development of FCE and CNV in choroidal osteoma.

Optical coherence tomography analysis of evolution of Bruch's membrane features in angioid streaks.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Evolving European guidance on the medical management of neovascular age related macular degeneration.

BACKGROUND: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)-thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. METHODS: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. RESULTS: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size

Quality of vision: A consensus building initiative for a new ophthalmologic concept.

PURPOSE: Many studies have addressed the quantification of visual acuity, and the conventional method of measuring it has so far demonstrated serious limitations. Vision testing requires new methods that can more precisely express the quality of vision as perceived by the patient. METHODS: This study employed the Delphi method of consensus building. Concepts associated with quality of vision (QoV) were identified by a board of experts and proposed to participating specialists in two subsequent questionnaires. Upon receipt of the completed questionnaires, the replies were classified to determine the building blocks of a consensus. RESULTS: By analyzing the replies to the two questionnaires, the authors determined the key elements of QoV on which a consensus was found among the respondents. CONCLUSIONS: A consensus was reached on the opinion that the quantification of visual acuity by traditional means is inadequate for investigating QoV. Although visual acuity is still a basic element for testing, the experts believe that contrast sensitivity, reading speed, and microperimetry are additional parameters necessary for quantifying QoV. The use of a psychometric questionnaire on visual function could allow a better interpretation of visual impairment.

Stellate nonhereditary idiopathic foveomacular retinoschisis concomitant to exudative maculopathies.

PurposeTo report the clinical course of patients presenting with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) concomitant with exudative maculopathies.MethodsRetrospective case series. Multimodal imaging findings, including spectral-domain optical coherence tomography (SD-OCT) were reviewed. Genetic testing for the RS1 gene was performed in one patient.ResultsWe identified two female patients who fit the definition of SNIFR and presented with concomitant neovascular age-related macular degeneration (n-AMD). In both the patients, SD-OCT showed exudative macular features and splitting (bilateral in patient 1, unilateral in patient 2) of the outer plexiform layer (OPL) in the macula with no other evidence of hereditary or an acquired predisposing condition. Genetic testing excluded mutation of RS1 gene in patient 1. The fundi of both the patients showed characteristic signs of active choroidal neovascularization (CNV) and following anti-VEGF treatment, visual acuity improved and CNV-related exudative changes resolved. However, the split along the OPL remained unaltered.ConclusionsSNIFR may be associated with n-AMD. It is important to recognise the presence of retinoschisis when there is other exudative pathology as the former may be misinterpreted as intraretinal fluid, prompting unnecessary treatment.

Optical Coherence Tomography Angiography of Diabetic Retinopathy.

PURPOSE: To describe the optical coherence tomography angiography (OCTA) features of diabetic retinopathy. METHODS: Literature review and case series. RESULTS: Four cases are presented. CONCLUSION: OCTA is an effective method for evaluating retinal changes in diabetic retinopathy and represents a novel complement or alternative to fluorescein angiography. Although OCTA should currently be considered an investigational technique, in the near future, it may play key roles in the diagnosis and management of diabetic retinopathy.

Spontaneous retinal pigment epithelium tear in geographic atrophy.

PURPOSE: To report two cases of spontaneous retinal pigment epithelial (RPE) tears occurring in two patients affected with geographic atrophy (GA) due to non-exudative age-related macular degeneration (AMD). CASE REPORT: Two patients (a 79-year-old man and a 71-year-old woman) presented to our department with progressive visual loss. The man had a best-corrected visual acuity (BCVA) of 20/100 in the right eye (RE) and 20/50 in the left eye (LE); the woman had a BCVA of 20/200 in the RE and 20/160 in the LE. Upon complete ophthalmologic examination, revealing a large area of atrophy (>175 µm in diameter) along with pigmentary changes, calcified drusen and no choroidal neovascularization (CNV) in either eye, the patients were diagnosed with GA due to non-exudative AMD. Interestingly, the imaging modalities performed, including fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT), clearly highlighted the presence of spontaneous RPE tears in the context of non-exudative AMD, while in general, RPE tears are a well-recognized complication of exudative AMD. CONCLUSIONS: To our knowledge, this is the first description of spontaneous RPE tears as a possible complication of GA due to non-exudative AMD.

Optical coherence tomography angiography in paracentral acute middle maculopathy secondary to central retinal vein occlusion.

PurposeTo report the clinical course and the optical coherence tomography angiography (OCTA) findings of patients presenting with paracentral acute middle maculopathy (PAMM) and central retinal vein occlusion (CRVO).MethodsRetrospective case series. Clincal records and multimodal imaging findings of patients presenting with PAMM and CRVO were reviewed.ResultsThree eyes of three patients (2 males; mean age: 66 years) were included in the study. Mean follow-up was 9 months and images using OCTA (AngioVue OCT angiography system, Optovue, Inc., Fremont, CA, USA) were available at the last follow-up visit. During follow-up, best corrected visual acuity (BCVA) of case 1 was unchanged at 85 ETDRS letters and OCTA revealed a mild attenuation of the perifoveal deep capillary plexus (DCP); in case 2, BCVA changed from 83 to 77 ETDRS letters and OCTA revealed patchy areas of attenuation and pruning of the DCP; in case 3, BCVA decreased from 26 to 8 ETDRS letters and OCTA revealed extensive areas of DCP dropout.ConclusionThe natural course of visual acuity in patients with PAMM secondary to CRVO may vary. In these patients, the extent of DCP dropout on OCTA may reflect the extent of visual acuity impairment.

"Light" versus "classic" laser treatment for clinically significant diabetic macular oedema.

AIM: To compare the effectiveness of "light" versus "classic" laser photocoagulation in diabetic patients with clinically significant macular oedema (CSMO). METHODS: A prospective randomised pilot clinical trial in which 29 eyes of 24 diabetic patients with mild to moderate non-proliferative diabetic retinopathy (NPDR) and CSMO were randomised to either "classic" or "light" Nd:YAG 532 nm (frequency doubled) green laser. "Light" laser treatment differed from conventional ("classic") photocoagulation in that the energy employed was the lowest capable to produce barely visible burns at the level of the retinal pigment epithelium. Primary outcome measure was the change in foveal retinal thickness as measured by optical coherence tomography (OCT); secondary outcomes were the reduction/elimination of macular oedema on contact lens biomicroscopy and fluorescein angiography, change in visual acuity, contrast sensitivity, and mean deviation in the central 10 degrees visual field. Examiners were masked to patients' treatment. RESULTS: 14 eyes were assigned to "classic" and 15 were assigned to "light" laser treatment. At 12 months, seven (50%) of 14 eyes treated with "classic" and six (43%) of 14 eyes treated with "light" laser had a decrease of foveal retinal thickness on OCT (p = 0.79). A comparison of reduction/elimination of oedema, visual improvement, visual loss, change in contrast sensitivity, and mean deviation in the central 10 degrees showed no statistical difference between the groups at 12 months (p>0.05 for all groups). CONCLUSIONS: This study suggests that "light" photocoagulation for CSMO may be as effective as "classic" laser treatment, thus supporting the rationale for a larger equivalence trial.