Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

Mid-term safety and effectiveness of intravitreal dexamethasone implant to treat persistent cystoid macular edema in vitrectomized eyes for bacterial endophthalmitis.

PURPOSE: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis. METHODS: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA). RESULTS: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357). CONCLUSION: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk.

Early treatment with dexamethasone intravitreal implants in diabetic macular edema: Naïve versus refractory patients.

PURPOSE: To assess the efficacy and safety of dexamethasone 0.7 mg implants (DEX-I) in patients with diabetic macular edema (DME) either naïve to therapy or refractory to anti-VEGF treatment, in a single-center, real-world setting. METHODS: Patients diagnosed with DME and treated with DEX-I were retrospectively enrolled in the study and split in two groups: naïve (Group 1, n = 64) and refractory (Group 2, n = 64) to treatment. Patients were evaluated at baseline, at 1 month, and every 3 months after each DEX-I implant. Main outcome measures were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to follow-up visits. RESULTS: Significant improvements in BCVA were observed in treatment-naïve patients at 6 months following the first and second DEX-I injection (p = 0.0023 and p = 0.0063, respectively), with significant reductions in mean CMT at 6 months after all DEX implants. In treatment-refractory patients, mean CMT was significantly reduced from baseline to 6 months (p < 0.05) after all DEX-I injections, although no changes were observed in BCVA. CONCLUSIONS: DEX-I improved visual acuity and macular edema mostly in treatment-naïve patients, suggesting DEX-I may be a viable first-line treatment option in DME.

Dexamethasone intravitreal implant in patients with cataract and naïve diabetic macular edema.

PURPOSE: To assess the feasibility and clinical effectiveness of dexamethasone intravitreal implant 0.7 mg (IDI) administered in diabetic patients to prevent the worsening of macular edema. METHODS: Forty eyes of 40 consecutive patients with naïve macular edema secondary to diabetes mellitus who were treated with IDI administered preoperative (Group A: 20 patients) or IDI administered immediately after cataract surgery (Group B: 20 patients). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes were evaluated at baseline and at postoperative time points. RESULTS: Follow-up study was 20 weeks. In Group A and B, mean BCVA improved significantly at all post-surgery time points (p < 0.05). In Group A and B, mean CMT decreased significantly at 16 weeks (p = 0.02 and p = 0.004, respectively). At week 20, CMT failed to reach statistical significance in both groups (p = 0.5, group A and p = 0.15, group B). No statistical differences were noted between groups in term of BCVA (with the exception of week 4 for the presence of cataract in Group A), CMT and IOP. CONCLUSIONS: The use of intravitreal dexamethasone implant 1 month prior to scheduled cataract extraction or at the time of phacoemulsification appears to be safe and effective for at least 16 weeks after surgery.

OUTER RETINAL TUBULATION: Characteristics in Patients With Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the incidence, characteristics, best-corrected visual acuity (BCVA), central macular thickness (CMT), and retinal sensitivity correlations in patients with and without outer retinal tubulation (ORT) affected by subfoveal choroidal neovascularization due to neovascular age-related macular degeneration. METHODS: Prospective case series including 78 eyes of 78 consecutive patients with subfoveal choroidal neovascularization due to neovascular age-related macular degeneration. Baseline and follow-up visits included BCVA, intraocular pressure, ophthalmoscopic examination, CMT as measured by spectral domain optical coherence tomography, and retinal sensitivity tested with fundus-related perimetry (MP-1). Fluorescent angiography was performed at baseline. RESULTS: At the end of the follow-up period, the mean BCVA and CMT of patients with ORT were statistically different from those without ORT (BCVA: 0.61 ± 0.13 vs. 0.37 ± 1.59, P < 0.0001; CMT: 290 ± 26.7 vs. 215.2 ± 33.5 µm; P < 0.0001). Patients with ORT showed a decreased mean retinal sensitivity compared with patients without ORT (6.31 ± 2.5 dB vs. 9.89 ± 5.43 dB; P < 0.0001). CONCLUSION: The results of this study investigating the BCVA, CMT, and retinal sensitivity detected by MP-1 between patients with and without ORT in neovascular age-related macular degeneration suggest that these parameters are statistically different in patients with ORT; this may be due to the pathogenesis of ORT formation, secondary to retinal pigment epithelial tears or photoreceptor damage. MP-1 microperimeter is a noninvasive instrument that provides useful information to better characterize the functional aspect of ORT in patients with age-related macular degeneration.

Lamellar macular hole following intravitreal pegaptanib sodium (Macugen) injection for diabetic macular edema.

To report on a patient who developed a lamellar macular hole 1 month after an intravitreal pegaptanib sodium injection. Interventional case report. A 66 year old patient developed a lamellar macular hole 1 month after an intravitreal pegaptanib sodium injection for diabetic macular edema (DME). The pathogenesis of the lamellar macular hole in our case can be attributed to the intravitreal injection that may have induced vitreous incarceration, causing vitreoretinal traction at the macula and development of a lamellar macular hole. Alternatively or in association, pegaptanib itself may have caused the lamellar macular hole by inducing sudden reduction of the DME and exacerbation of tangential traction of the posterior vitreous on the overlying macular retina. Lamellar macular hole seems to be a potential complication of pegaptanib injection even in patients without pretreatment clinically detectable vitreomacular traction.

Very Large Bilateral Lesions Obscuring Diagnosis of Adult-Onset Foveomacular Vitelliform Dystrophy.

Adult-onset foveomacular vitelliform dystrophy (AFVD) is a clinically heterogeneous and pleomorphic disease originally described by Gass as bilateral with symmetrical, solitary, round or oval, slightly elevated, yellowish subretinal lesions, one third to one disc diameter in size, often with a central pigmented spot. A possible AFVD patient showing very large bilateral macular lesions was reported.

High-Definition OCT Findings in Acute Posterior Multifocal Placoid Pigment Epitheliopathy.

The authors report a case of acute posterior multifocal placoid pigment epitheliopathy evaluated by autofluorescence, fluorescein angiography, indocyanine green angiography, high-definition optical coherence tomography, and microperimetry in both the acute and the post-acute phase. Based on the integrated findings, the authors believe that acute posterior multifocal placoid pigment epitheliopathy is an inflammatory disease that primarily affects the choroid and that the retinal pigment epithelium is secondarily involved in the course of the disease.

Local resection versus combined local resection and plaque radiotherapy in the treatment of choroidal melanoma.

PURPOSE: To evaluate the outcome of local resection versus combined local resection and plaque radiotherapy in the treatment of choroidal melanoma. METHODS: We retrospectively analyzed the records of 60 patients (60 eyes) managed by local resection (group 1, 30 patients, external or internal local resection) or combined local resection and plaque radiotherapy (group 2, 30 patients, both Ruthenium-106 or Cobalt-60), among the 364 melanomas treated at our Department of Ophthalmology, between January 1980 and December 2006. Main outcomes measures were postsurgical complications, visual acuity, local recurrence, reasons for enucleation, and development of metastasis. RESULTS: The 2 groups of patients were considered sufficiently homogeneous as regards location, cell type, and age. Mean follow-up was 7 years. The median largest basal tumor diameter was 9.8 mm and 10.1, and the median tumor thickness was 7.9 mm and 8, respectively, in groups 1 and 2. No statistically significant differences resulted between group 1 and group 2 as regards postsurgical complications (vitreous hemorrhage, retinal detachment, maculopathy, cataract, and optic neuropathy) (p>0.05), visual acuity (p>0.05), local recurrence (p>0.05), reasons for enucleation (p>0.05), or development of metastasis (p>0.05). CONCLUSIONS: No adjunctive benefits from the combined local resection and plaque radiotherapy can be ruled out from our study.

Intravitreal pegaptanib sodium (Macugen) for diabetic macular oedema.

PURPOSE: To report the functional and anatomical outcomes resulting from the use of intravitreal pegaptanib sodium (Macugen) in patients with diabetic macular oedema (DMO). METHODS: We conducted a retrospective outcome analysis, by optical coherence tomography (OCT) and best-corrected visual acuity (BCVA), of eyes with DMO treated with intravitreal pegaptanib sodium. Moreover, we evaluated the foveal transverse photoreceptor (PR) band integrity in the OCT images at the time of the last follow-up visit. RESULTS: Sixty-three eyes of 48 patients with a minimum of 6 months of follow-up were included for analysis. Intravitreal pegaptanib was found to produce significant improvements in mean BCVA (p = 0.019) and reductions in mean central macular thickness (CMT) (p < 0.001) as soon as the 6-week follow-up. Most eyes (60/63) required a mean of 3.03 +/- 0.9 repeated treatments, over a mean follow-up period of 6.7 +/- 1.2 months, to achieve significant improvements in mean BCVA (p < 0.001) and mean CMT (p < 0.001). In our series, the lower visual acuities tended to congregate in the group with the less-defined PR band (p < 0.001) and the lower CMT tended to congregate in the group with the best-defined PR band (p = 0.04), even though the higher CMT did not tend to congregate in the group with the less-defined PR band. CONCLUSION: Our findings demonstrate that selective inhibition by intravitreal pegaptanib sodium of vascular endothelial growth factor (VEGF)-165 may produce a clinically meaningful and statistically significant benefit in the treatment of DMO.

Short-term fluctuation of diabetic macular edema after intravitreal ranibizumab injection.

PURPOSE: To examine the short-term fluctuation of diabetic macular edema (DME) after one intravitreal ranibizumab injection. METHODS: Twenty consecutive patients with DME received an intravitreal injection of ranibizumab (0.05 mL/0.5 mg). Assessment of best-corrected visual acuity (BCVA), fundus biomicroscopy, MP-1 fundus-related perimetry using follow-up strategy (pattern macula 8 degrees 0 dB with threshold strategy 4-2), and optical coherence tomography central macular thickness (CMT),were performed at baseline and 1 hour, 24 hours, 14 days, 28 days, and 56 days after intravitreal injection of ranibizumab. RESULTS: A total of 18 eyes of 18 patients (9 male, 9 female; mean age, 62.28 +/- 8.08 years; range, 48-75 years) who completed the 56-day follow-up were included for analysis. Intravitreal ranibizumab was found to produce significant improvements in mean BCVA and MP-1 sensitivity, as well as reduction in mean CMT, after one injection. This anatomical and functional improvement, which compared with baseline was evident as soon as the 1-hour follow-up (mean CMT reduction: t= 1.7899, P = 0.045; mean MP-1 sensitivity improvement: t = -1.9891, P 0.0315), and lasted until the 56-day follow-up (mean BCVA improvement: t= 2.26, P < 0.05; mean CMT reduction: t = 3.61, P < 0.05; MP-1 sensitivity improvement: t = -5.21, P < 0.05). CONCLUSION: These short-term observations give insights into the physiopathology of DME treated with a intravitreal ranibizumab injection.

Intravitreal pegaptanib sodium (Macugen) for refractory cystoid macular edema in pericentral retinitis pigmentosa.

The purpose of this paper was to describe a patient with pericentral retinitis pigmentosa (RP) and cystoid macular edema (CME) refractory to oral acetazolamide alone who was successfully treated with adjunctive pegaptanib sodium. A 33-year-old man presented with decreased vision and a best-corrected visual acuity (BCVA) in his left eye of 20/200 due to CME secondary to RP. Although he had been treated daily for 1 month with 500 mg of oral acetazolamide, the edema was unresponsive. When informed of the available treatment options, the patient requested adjunctive intravitreal pegaptanib sodium. One month after receiving an injection of pegaptanib sodium 0.3 mg and continued daily acetazolamide, the patient's BCVA had improved to 20/40. At the 4-month follow-up visit, no recurrence of CME was found on fundus biomicroscopy, fundus-related perimetry, and optical coherence tomography. We conclude that intravitreal pegaptanib sodium combined with daily doses of acetazolamide appears to provide benefits in CME refractory to oral acetazolamide alone with regards to the improvement of visual acuity.

Isolated foveal hypoplasia.

PURPOSE: To describe a patient with isolated foveal hypoplasia. METHODS: A 55-year-old man with the clinical suspicion of foveal hypoplasia was given a complete ophthalmological examination, including optical coherence tomography (OCT), fluorescein angiography (FA) and fundus-related perimetry (FRP). Mutation screening for oculocutaneous albinism and aniridia was also performed, but the results were negative for both. RESULTS: Following a complete ophthalmological examination and genetic studies, we were able to confirm the clinical suspicion of isolated foveal hypoplasia in this otherwise healthy patient. CONCLUSIONS: With this report we want to highlight the roles of OCT, FA and FRP in the diagnosis of such a singular condition as isolated foveal hypoplasia.

Successful treatment of pseudophakic cystoid macular edema with intravitreal bevacizumab.

A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME) after uneventful phacoemulsification. Three months after an intravitreal injection of bevacizumab (1.25 mg), the CME was completely resolved, with resultant improvement in visual acuity.

Correlation of visual function impairment and optical coherence tomography findings in patients with adult-onset foveomacular vitelliform macular dystrophy.

PURPOSE: To investigate the relationship between morphologic and functional abnormalities in patients affected with adult-onset foveomacular vitelliform macular dystrophy (AFVD). DESIGN: Prospective, noncomparative observational study. METHODS: A complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus examination, fundus-related perimetry, and optical coherence tomography (OCT), was performed in 20 consecutive AFVD patients. The stage of the disease and the thickness of the neuroepithelium at the foveola (neurosensory retina) were compared with the BCVA as well as with the type of scotoma, the average retinal sensitivity, and the location and stability of fixation. RESULTS: Thirty-five eyes of 20 consecutive patients (10 men and 10 women; mean age, 58.2 years) were graded as follows: 10 had vitelliform stage (stage 1), nine had pseudohypopyon stage (stage 2), 10 had vitelliruptive (stage 3), and six had atrophic stage (stage 4) disease. Reduced thickness of the neuroepithelium at the foveola and BCVA were statistically correlated to an advanced stage of the disease (P = .001 and P = .0062, respectively). Moreover, worse BCVA was correlated statistically to reduced thickness of the neuroepithelium at the foveola (r = 0.14; P = .02). Reduced thickness of the neuroepithelium at the foveola was correlated statistically to the development of absolute scotoma (P = .03), eccentric fixation (P = .01), and unstable fixation (P = .03). CONCLUSIONS: OCT and fundus-related perimetry allow a correlation to be defined between foveal thickness and visual function and are useful tools to define better the degree of anatomic and functional impairment in AFVD patients.

Residual bubble of oxane hd: a study by optical coherence tomography and fundus-related perimetry.

PURPOSE: Oxane HD is a mixture of silicone oil and a mixed fluorinated and hydrocarbonated olefin. The authors report a complication of Oxane HD as internal tamponade after removal of all visible heavy silicone oil. METHODS: A 71-year-old man who underwent vitrectomy with Oxane HD presented with adherence of a residual bubble of Oxane HD in the macula after removal of all visible heavy silicone oil. In this patient OCT displayed an optical artifact due to the residual bubble, and fundus-related perimetry revealed a predominantly eccentric and relatively unstable fixation and very low macular sensitivity. RESULTS: After surgical removal of the residual bubble, metamorphopsia resolved, sensitivity improved as revealed by fundus-related perimetry, and fixation became predominantly central and more stable. CONCLUSION: The authors suggest a way to manage this rare complication of Oxane HD as internal tamponade after removal of all visible heavy silicone oil.

Focal laser photocoagulation for polypoidal choroidal vasculopathy associated with choroidal nevus.

PURPOSE: To describe a patient treated with focal laser photocoagulation for polypoidal choroidal vasculopathy (PCV) secondary to choroidal nevus. METHODS: A 62-year-old woman presented with PCV secondary to choroidal nevus in the right eye and best-corrected visual acuity of 20/100. The polypoidal lesions were treated with focal laser photocoagulation and clinical and instrumental data were prospectively analyzed. RESULTS: Three months after focal laser photocoagulation, fluorescein angiography showed no leakage from the polypoidal lesions, optical coherence tomography scans displayed absence of subretinal fluid, and visual acuity improved to 20/25 and remained stable throughout an 18-month follow-up. CONCLUSION: Focal laser photocoagulation seems to be an effective and safe treatment for PCV secondary to choroidal nevus.

Combined central retinal vein and cilioretinal artery occlusion.

We present a case of combined central retinal vein and cilioretinal artery occlusion which, due to the absence of the temporal branch retinal artery, was initially misdiagnosed as a combined central retinal vein occlusion and temporal branch retinal artery occlusion. Given that--in contrast to cases of combined central artery and central retinal vein occlusion--the prognosis for cilioretinal artery occlusion with central retinal vein occlusion is quite good, this case illustrates the importance of suspecting an unusual condition in the presence of a combined occlusion.