Mary Romano

Diabetic Retinopathy: Vascular and Inflammatory Disease

Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted.

Intravitreal bevacizumab for treatment-naive patients with subfoveal occult choroidal neovascularization secondary to age-related macular degeneration: a 12-month follow-up study.

Purpose: The aim of this study was to assess the 12-month efficacy of intravitreal bevacizumab (IVB) injection for occult choroidal neovascularization secondary to age-related macular degeneration. Methods: In this retrospective, interventional case series, 68 treatment-naïve patients with age-related macular degeneration, affected by subfoveal occult choroidal neovascularization showing recent disease progression, were monitored during the IVB protocol. The patients received 1 initial IVB injection (1.25 mg/0.05 mL), and they underwent further retreatment on a monthly basis only when necessary, according to a standardized as-required regimen, until no significant signs of choroidal neovascularization activity were present. Main outcome measures were the modifications in best-corrected visual acuity and in central retinal thickness measured by optical coherence tomography. Results: With respect to baseline, at the 12-month check, mean best-corrected visual acuity increased from 0.82 to 0.45 logMAR (P < 0.01) and mean central retinal thickness decreased from 517.0 &mgr;m to 306.5 &mgr;m (P < 0.01). To achieve these benefits, the required mean IVB number was lowered from 3.87 in the first 6 months to 1.085 in the second 6 months. A better final best-corrected visual acuity was correlated with greater best-corrected visual acuity (P < 0.005) and lesser central retinal thickness (P < 0.05) at baseline. Conclusion: In patients with age-related macular degeneration complicated by progressive occult choroidal neovascularization, first-line IVB administration represents a useful therapeutic option, especially considering its lower cost in comparison with other antiangiogenic drugs.

12-month retrospective study and review of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.

Purpose: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. Methods: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. Results: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P < 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. Conclusions: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.

Macular Hypotrophy After Internal Limiting Membrane Removal For Diabetic Macular Edema

Purpose: To compare the anatomic and functional effects of three different approaches to nontractional diabetic macular edema. Methods: Retrospective comparative study. Sixty eyes of 60 patients diagnosed with cystoid diabetic macular edema and treated with 1.25 mg/mL intravitreal bevacizumab (Group A), laser photocoagulation (Group B), or vitrectomy with inner limiting membrane peeling (Group C) were included in the study. Changes in number of Early Treatment Diabetic Retinopathy Study letters, central macular thickness, largest diameter of the intraretinal cysts (IC), and choroidal thickness were investigated. Analyses were performed during follow-up visits at Months 1, 3, 6, 9, and 12. Results: Visual acuity only significantly improved in Group A at the last follow-up (P = 0.004). Central macular thickness significantly decreased in every group throughout the follow-up period. Differences in central macular thickness between Groups A and B (P < 0.01), A and C (P < 0.01), and B and C (P < 0.01) were significant. Intraretinal cysts also significantly decreased in each group throughout the follow-up period. Differences in IC size between Groups A and B (P = 0.8), A and C (P = 0.1), and B and C (P = 0.1) were not significant. Choroidal thickness did not undergo any significant change in any group throughout the follow-up period. A significant correlation was also found in Group A between best-corrected visual acuity at month 12 and baseline central macular thickness (R = 0.3; P = 0.006), and in Group B between postoperative best-corrected visual acuity at month 12 and baseline IC size (R = 0.8; P < 0.01, negatively correlated at 92.4%). Conclusion: According to our retrospective data, diabetic macular edema with intraretinal cysts larger than 390 &mgr;m should not be treated with vitrectomy with ILM peeling, because this may induce subfoveal atrophy, defined as the “Floor Effect,” and subsequent visual deterioration.

Vitreo-papillary adhesion as a prognostic factor in pseudo- and lamellar macular holes

PurposeTo determine the incidence of vitreopapillary adhesion (VPA) and to investigate its value as a prognostic factor in the surgical outcome of pseudo- (PMH) and lamellar macular holes (LMH).MethodsA total of 76 consecutive patients, diagnosed with PMH (41 eyes) or LMH (35 eyes) were included. Eyes with VPA were alternatively assigned to the surgical or control group. Surgery consisted of a 25G vitrectomy and internal limiting membrane peeling with blue dye staining. There were six visits: baseline, the day of surgery, and 1, 3, 6, and 9 post-operative months. Main outcome measures were the incidence of VPA and changes in the outer retinal layers and visual acuity.ResultsVPA was found in 27% (11/41) of patients with PMH and 37% (13/35) with LMH (P=0.03). In presence of VPA, the best-corrected visual acuity (BCVA) improved in the surgery group from 32±8 to 47±8 letters, whereas the control group went from 34±7 to 31±8 letters. The difference in letters between the surgery and control groups was statistically significant for both distance (P=0.032) and near (P=0.04) vision. Intra-retinal cysts were significantly correlated with a poor functional prognosis (P=0.01). We found the presence of focal damage to the outer retinal layers in LMH and PMH.ConclusionVPA is more frequent in the presence of LMH vsPMH. It significantly influences the tangential forces at the vitreoretinal interface, exacerbating anatomical changes, and worsening the functional prognosis. Functional difference between the surgical and control groups was statistically significant for distant and near vision in presence of VPA.

Intravitreal infliximab for choroidal neovascularization in patients refractory to conventional treatments.

The aim of the study is to evaluate the effectiveness and safety of intravitreal infliximab in the course of compassionate use in patients affected by choroidal neovascularization. This prospective interventional case series includes four eligible patients, affected by exudative age-related macular degeneration (2/4), retinal angiomatous proliferation (1/4) and central retinal vein occlusion (1/4), who were refractory to conventional treatments. The patients received a single intravitreal injection of 0.05 ml of reconstituted infliximab solution (20mg/ml). The main outcomes measure were changes in best-corrected visual acuity and central retinal thickness. Patients were evaluated at baseline, every week for the first month, then every two weeks, and on demand. Morphologic parameters improved after a single infliximab intravitreal injection. However, all patients developed acute uveitis in a period ranging from 4 to 7 weeks after treatment. Control of the intraocular inflammation was achieved with topical and systemic steroids in 3 patients, whereas in one case pars plana vitrectomy was needed. A single intravitreal injection of infliximab does not seem to improve the natural history of CNV from different aetiologies. However, all patients in our series developed a serious inflammatory response that required surgical management in one case. The intravitreal administration of infliximab is hence not safe and not recommended in clinical practice.

Verteporfin photodynamic therapy for subfoveal choroidal neovascularization in pathologic myopia: a 12-month retrospective review

Purpose To evaluate the visual outcome of patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia treated with verteporfin photodynamic therapy (PDT-V) and to verify the predictive role of visual and angiographic parameters. Methods This is a retrospective, interventional, consecutive case series study of subjects with subfoveal CNV secondary to pathologic myopia. All patients received PDT-V according to VIP guidelines. A complete ophthalmologic evaluation was performed on all patients and included best-corrected visual acuity (BCVA), fundus examination, and fluorescein angiography (FA, IMAGEnet System, Topcon Corp., Japan). CNV size (mm2) was directly measured on the early phase of the angiogram using the software included with the IMAGEnet package. All checks were scheduled at 3-month intervals for a period of 1 year. A review of medical and angiographic records was performed and assessed throughout a 12-month follow-up period. Results A total of 62 patients (62 eyes) were examined. Best-corrected visual acuity (BCVA) moderately decreased without reaching a statistically noticeable level throughout the follow-up; reduction in lesion size reached a significant level at the second checkup. A significant correlation between higher baseline BCVA and better final visual outcome was detected. Conclusions Standardized PDT-V minimizes central vision deterioration in patients with CNV secondary to pathologic myopia. Better BCVA at presentation represents a good predictive sign.

Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: a long-term follow-up study

Purpose To evaluate the safety and efficacy of intravitreal bevacizumab (IVB) to treat choroidal neovascularization (CNV) in patients with angioid streaks. Methods Retrospective chart review of 16 eyes of 10 patients treated with IVB for CNV secondary to angioid streaks between November 2005 and November 2011. Intravitreal bevacizumab was performed in all patients with a pro re nata regimen. Seven eyes received an additional photodynamic therapy and 1 eye argon laser photocoagulation. The diagnosis of CNV was confirmed by fluorescein angiography (FA) and indocyanine green (ICG) angiography; central macular thickness (CMT) was evaluated by optical coherence tomography. Outcome measures included changes in best-corrected visual acuity, retinal thickness, and degree of leakage on FA and ICG angiography. Results The median number of IVB was 2.5 (range 1-6) during a mean follow-up of 52 months (range 30-67). Risk of recurrence increased during the first 50 weeks; then it remained stable. In 6 of 16 eyes, the CNV was obliterated with a single injection. Increasing CNV reactivation corresponded with an increased number of injections. Final visual acuity was related to initial VA and not to number of injections or shorter follow-up. Previous treatments, CMT, or baseline CNV size were not related to final visual acuity. Conclusions Intravitreal bevacizumab proved to be well-tolerated in patients with CNV secondary to angioid streaks and in our small cohort IVB was efficacious for long-term follow-up. Larger series of patients are needed to confirm the effects of this treatment.

Branch retinal artery embolization due to calcific aortic valve stenosis.

Purpose. Branch retinal artery occlusion caused by calcific embolization secondary to calcific aortic valvulopathy Methods. A 45-year-old woman came to our attention complaining a sudden painless loss of her peripheral superior visual field. Best visual acuity was 20/20. Fundus examination revealed the presence of a retinal arterial embolic occlusion of the inferior branch. Fundus retinography visual field, and fluorescein angiography were performed and medical therapy was started. The echocardiography examination revealed a tricuspid and calcified aortic valve with moderate stenosis and regurgitation. Due to the heart pathology, the patient moved to the cardiosurgery department, where an aortic valve replacement was performed. Results. Four months after cardiac surgery, visual acuity of both eyes was stable (20/20). Fundus examination showed a complete reabsorption of the retinal edema and the resolution of retinal pallor. Fluorescein angiography confirmed the delay of the arterial filling. No retinal ischemia was observed. The visual field examination confirmed the deep scotoma previously registered. Conclusions. Retinal arterial embolization is a rare but potentially devastating complication of calcific aortic stenosis. Initial retinal presentation of calcific aortic stenosis is a rare condition. Keeping in mind that these emboli may be recurrent and potentially bilateral, a sudden onset of visual field defects, especially in young asymptomatic patients, needs immediate diagnosis and consideration of an urgent surgical correction.

Comment on, 'Factors affecting outcomes of corneal collagen crosslinking treatment'

Sir, We read with great interest the article by Toprak et al1 regarding the evaluation of possible preoperative predictive factors influencing the outcome of cross-linking (CXL) in a group of 96 patients with progressive keratoconus (KC). The authors conclude that an older age (≥30 years), a worse corrected distance visual acuity (CDVA; ≤20/40), and a thinner corneal pachimetry (<450 μm) were positive predictive factors for CXL, whereas maximum K (Kmax) did not affect the postoperative change. Although we agree that age influences the outcome of the treatment,2 our results, stratified into four subgroups (<18 years, 18–28 years, 29–39 years, and over 40 years), demonstrated a better functional and morphological outcomes in the population between 18 and 39 years of age. Furthermore, here we report a subset analysis of the data evaluated in Ophthalmology2 based on preoperative curvature and thinnest corneal thickness (ThCT). In particular, the data have been stratified according to preoperative Simk1 ( 5 0D) and ThCT ( 450 μm). Comparative analysis between curvature subgroups indicated the subgroup over 50 D as the best responder with a significant improvement in CDVA (P<0.05) and in total aberration outcomes (P<0.05; Figures 1a and b). Analysis based on ThCT showed a better reaction to CXL in the subgroup <400 μm with a significant difference in sphere change (P<0.05; Figure 1c). Figure 1 Box and whisker plot between follow-up and preoperative values with respect to preoperative curvature (a and b) and thickness (c). Differences divided by preoperative Simk1 for best-corrected visual acuity (BCVA) are shown in graph a, for total aberration ... These results are in partial agreement with that of Greenstein et al,3 which showed that patients with a preoperative Kmax≥55 D were more likely to have flattening ≥2 D. Our main finding shows that eyes with progressive KC with higher curvature (>50 D) and low pachymetry (<400 μm), representing more advanced cases, are more likely to have an improvement after CXL. Moreover, we would like to comment on the reported use of the isotonic riboflavin solution. It has been demonstrated that, in advanced KC (with thin corneas), using a standard isotonic solution, dextran, induces a decrease of thickness (CCT) that can cause endothelial damage and deep stromal opacities.4 To avoid these complications it is advisable to check intraoperative CCT and in case of the thickness reducing <400 μm, use swelling solutions.2 Vetter et al5 in a recent report did not find a correlation between osmolality and CCT after riboflavin eye drop application but found an inverted correlation between dextran concentration and CCT. The authors explained that hypertonicity and hypotonicity of solutions do not have a significant effect on stromal thickness because only 2–3% of the corneal stroma volume consists of cells, conversely dextran possesses a high affinity for water because of its abundant hydrophilic hydroxyl groups leading to deswelling beyond the physiological level. For this reason we suggest to evaluate not only the osmolality of the solution but also the concentration of dextran. In conclusion, our report confirmed the literature finding that a preoperative high keratometry is a positive predictive factor. Furthermore, our findings add that keratoconic corneas with very low pachymetry are more likely to improve. For this reason we suggest to treat advanced KC also and in case of ThCT <400 μm to use swelling solutions.