Rosa Dolz-Marco

Oxidative stress and its downstream signaling in aging eyes

Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.

Quantitative OCT Angiography of the Retinal Microvasculature and the Choriocapillaris in Myopic Eyes

Purpose To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using quantitative optical coherence tomography angiography (OCTA) analysis. Methods Macular OCTA images of 3 × 3 mm were obtained using the RTVue-XR Avanti with AngioVue. Quantitative measurements of the retinal capillary microvascular layers and the CC were analyzed using en face projection images. Vessel density and fractal dimension of the superficial and deep retinal capillary plexus, and area and density of flow reduction in the CC were analyzed, quantified, and compared with an age-matched control group. Results Fifty eyes with myopia and 34 age-matched healthy eyes were included in this study. The vessel density and the vessel branching complexity using fractal dimension of the retinal capillary microvasculature were significantly lower in myopic eyes (P < 0.001 and P = 0.001). The total number of flow voids in the CC was lower (108.93 vs. 138.63, P = 0.001) but the total and average flow void area was significantly higher (total area 3.715 ± 0.257 vs. 3.596 ± 0.194 mm2, P = 0.026; average area 0.044 ± 0.029 vs. 0.028 ± 0.010 mm2, P = 0.002) compared with the healthy control group. Average choroidal thickness was lower in the myopic group versus the normal control cohort (123.538 ± 73.477 vs. 246.97 ± 41.745 μm, P < 0.05) and significantly reduced in eyes with lacquer cracks (LC) compared with myopic eyes without LC formation (P = 0.003). There was no correlation between choroidal thickness and quantitative parameters of the CC in the myopic eyes. Conclusions The density of the retinal capillary microvasculature is reduced and the area of flow deficit in the CC is increased in eyes with greater myopia. The relevance of microvascular alterations in the setting of myopia warrants further study.

Smoking and Age-Related Macular Degeneration: Review and Update

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

Update on the principles and novel local and systemic therapies for the treatment of non-infectious uveitis.

Ocular inflammatory disorders constitute a sight-threatening group of diseases that might be managed according to their severity. Their treatment guidelines experience constant changes with new agents that improve the results obtained with former drugs. Nowadays we can make use of a five step protocol in which topical, periocular and systemic corticosteroids remain as the main therapy for non-infectious uveitis. In addition, immunosuppresive drugs can be added in order to enhance the anti-inflammatory effects and to play the role of corticosteroid-sparing agents. These can be organized in four other steps: cyclosporine and methotrexate in a second one; azathioprine, mycophenolate and tacrolimus in a third step; biological anti-TNF drugs in fourth position; and a last one with cyclophosphamide and chlorambucil. In the present review we go through the main characteristics and complications of all these treatments and make a rational of this five-step treatment protocol for non-infectious posterior uveitis.

Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy

Purpose We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). Methods A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. Results The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 × 10-3) and deep (P = 2.653 × 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 × 10-5) and deep (P = 3.120 × 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. Conclusions The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.

INTRAVITREAL DEXAMETHASONE IMPLANT FOR THE TREATMENT OF REFRACTORY MACULAR EDEMA IN RETINAL VASCULAR DISEASES: Results of the KKESH International Collaborative Retina Study Group.

Purpose: To evaluate the safety and efficacy of intravitreal dexamethasone implant (Ozurdex) for treating refractory macular edema in retinal vascular diseases. Methods: This is a retrospective consecutive series of 53 eyes with refractory macular edema secondary to central retinal vein occlusion (13 eyes), branch retinal vein occlusion (14 eyes), and diabetic macular edema (26 eyes) treated with a single 0.7 mg dexamethasone implant. Data were collected on best-corrected visual acuity, intraocular pressure, and central macular thickness preoperatively and at 1, 3, and 6 months postoperatively. Results: Baseline best-corrected visual acuity was 20/160 and improved statistically significantly to 20/80 and 20/60 at 1 months and 3 months, respectively (P < 0.05, both postoperative visits), and 20/100 at 6 months (P > 0.05). The central macular thickness at baseline was 569.96 ± 178.11 &mgr;m, and it decreased statistically significantly to 305.81 ± 155.94 &mgr;m, 386 ± 210.79 &mgr;m, and 446.41 ± 221.21 &mgr;m at 1, 3 and 6 months, respectively (P < 0.05, all visits compared with baseline). Fourteen (26%) eyes developed high intraocular pressure after implantation and was successfully controlled with topical medications, and cataract progressed in 1 (1.8%) eye. Conclusion: The dexamethasone implant improved macular edema in refractory cases resulting in statistically significant improvements in best-corrected visual acuity and central macular thickness that remained stable to 3 months and 6 months, respectively.

Serous macular detachment associated with dome-shaped macula and tilted disc.

Introduction: An entirely new type of staphyloma has been recently described as dome-shaped macula (DSM). It is characterized by an abnormal convex macular contour within the concavity of a posterior staphyloma. We found DSM associated with serous macular detachment (SMD) and tilted disc in two consecutive cases. Case Reports: Case 1: A 37-year-old female presented to our department because of sudden onset blurred vision in her right eye (OD). The best-corrected visual acuity (BCVA) was 0.5 in both eyes. Funduscopy evidenced bilateral tilted disc associated with posterior staphyloma. Optical coherence tomography (OCT) demonstrated a DSM with SMD in her OD. After 15 months of follow-up, BCVA of her OD remained stable with chronic SMD. Case 2: A 32-year-old female presented to our department because of blurred vision in her OD. The BCVA was 0.4 in the OD and 1.0 in the left eye (OS). Bilateral tilted disc and posterior staphyloma were evidenced in the funduscopy. OCT demonstrated a bilateral DSM with SMD in her OD. After 45 months of follow-up, two further episodes of transient SMD were observed in her OD and seven in her OS. The final BCVA was 0.63 in the OD and 0.8 in the OS. Discussion: SMD associated with tilted disc constitutes a potential cause of subretinal fluid accumulation in myopic patients. OCT is essential for the detection of both SMD and DSM.

Optical Coherence Tomography Angiography in Fovea Plana.

Fovea plana is characterized by the anatomical absence of the foveal pit in eyes with normal visual function. The authors have analyzed three cases of idiopathic fovea plana with optical coherence tomography angiography (OCTA). As previously reported, the authors found the absence of a foveal avascular zone in all cases with OCTA; however, a preserved fusion of both the superficial and the deep capillary plexuses was found around the foveal center. This novel observation cannot be detected with conventional dye-based angiography, in which the deep capillary plexus is not visualized. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:670-673.].

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SHOWS INNER CHOROIDAL ISCHEMIA IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

Purpose: To describe multimodal imaging findings of an evolving case of acute posterior multifocal placoid pigment epitheliopathy occurring in a young healthy male. Methods: Case report of a patient with acute posterior multifocal placoid pigment epitheliopathy including comprehensive systemic and ocular examinations. Ultra-widefield autofluorescence, fluorescein angiography, indocyanine green angiography, and serial optical coherence tomography angiography were performed. Results: A 34-year-old male presented with acute vision loss in his left eye for 2 weeks. His best-corrected visual acuity was 20/20 in his right eye and 20/200 in his left eye. Dilated funduscopic examination revealed multiple creamy white deep retinal lesions showing macular involvement of the left eye with a diffuse area of pigmentary changes. The presence of multiple areas of hypoperfusion of the inner choroid were demonstrated with fluorescein and indocyanine green angiography. Serial optical coherence tomography angiography showed multiple evolving areas of decreased flow at the level of the inner choroid. Conclusion: Although the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains unknown, there is growing evidence of a primary choroidal involvement with secondary damage to the overlying retinal pigment epithelium and the outer retinal layers. Optical coherence tomography angiography may provide valuable information for the diagnosis and follow-up of this condition avoiding invasive angiographic procedures.

Update on intravitreal anti-tumor necrosis factor alpha therapies for ocular disorders

Tumor necrosis factor alpha (TNF-?) is an important pro-inflammatory cytokine associated with a variety of ocular diseases. The currently available TNF-? inhibitors are etanercept, infliximab, adalimumab, golimumab, and certolizumab. Experimental and clinical studies on the intravitreal use of these agents have been reported with etanercept, infliximab, and adalimumab: etanercept has shown limited efficacy in scarce reports; infliximab has been associated with local safety concerns but appears to benefit certain cases; adalimumab has shown no efficacy in cases of age-related macular degeneration (AMD) or diabetic macular edema (DME), but the combination with bevacizumab may be effective in refractory cases of macular diseases. Further preclinical and clinical studies are warranted in order to be able to obtain a more robust conclusion on the use of intravitreal TNF-? inhibitors.