Intravitreal fasudil monotherapy for treatment of refractory diabetic macular edema: A prospective interventional case series.

BACKGROUND: Suboptimal response to conventional treatments in refractory diabetic macular edema (rDME) encourages efforts to identify new therapeutic options. PURPOSE: To evaluate the effect of three monthly intravitreal injections of a Rho-associated protein kinase (ROCK) inhibitor (Fasudil, Asahi Kasei Pharma Corporation, Tokyo, Japan) in eyes with rDME. METHODS: Ten eyes of 10 patients with DME unresponsive to at least six previous intravitreal bevacizumab (IVB) injections were recruited and underwent 3 consecutive monthly intravitreal injection of 0.025mg/0.05mL Fasudil. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated as functional and anatomical response indicators, respectively. RESULTS: The mean age was 60.1±5.1 years (range, 53-68). Five cases responded to treatment, two with both anatomical and functional responses (reduction of CMT from 521 to 395 and from 390 to 301 microns and improvement of BCVA from 0.3 to 0.1 LogMAR and 0.6 to 0.4 LogMAR, respectively) and three with only functional improvement (0.7 to 0.4; 0.7 to 0.4; and 0.3 to 0.1 LogMAR). Of note, cases with no significant change in CMT showed morphologic improvement of the retinal microstructure to some extent. No adverse event was observed during the study period. CONCLUSION: Monotherapy with intravitreal injection of ROCK inhibitors appears to have moderate visual benefits in eyes with DME refractory to IVB. Such effects may be functionally significant without obvious anatomical improvement.

A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome.

PurposeJalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation.Patients and MethodsA seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations.ResultsOcular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electro-retinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects.ConclusionWe identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.

Single-session photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.

PURPOSE: To evaluate the efficacy of combined single-session photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) for treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective interventional case series, patients with subfoveal choroidal neovascularization (CNV) underwent PDT followed by 1.25 mg IVB injection. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were repeated at 6-week intervals and fluorescein angiography was performed after 12 weeks and when considered necessary thereafter. Repeat injections of IVB were performed based on fluorescein angiographic evidence of CNV leakage. RESULTS: Fourteen eyes were included in this study. Mean follow-up was 52.4+/-15.2 weeks (range: 26-74 weeks). Initially, mean BCVA was 0.80+/-0.42 logMAR and mean central macular thickness (CMT) was 308+/88 microm. At week 12, BCVA improved to 0.62+/-0.47 logMAR (p=0.006) and CMT reduced to 186+/-53 microm (p=0.003). Corresponding results were 0.53+/-0.52 logMAR (p=0.02) and 193+/-78 microm (p=0.002) after 24 weeks. A second IVB injection was performed in 13 eyes with a mean interval of 16.3+/-5.9 weeks. CONCLUSIONS: Combination therapy with single-session PDT and IVB can improve vision and reduce CMT in neovascular AMD. Repeat IVB injections may maintain the visual gain from the initial combination therapy.

Posterior sub-tenon triamcinolone for refractory diabetic macular edema: a randomized clinical trial.

PURPOSE: To evaluate the effect of posterior sub-tenon triamcinolone acetonide (TA) injection on clinical, angiographic, and optical coherence tomographic (OCT) parameters in refractory diabetic macular edema (DME). METHODS: In a double-masked placebo-controlled clinical trial, 64 eyes were randomly assigned to two groups. The treatment group (32 eyes) received 40 mg posterior sub-tenon injection of TA and the placebo group (32 eyes) received subconjunctival injection of a placebo. The injections were repeated after 2 months in both groups. Complete ophthalmologic examination, fluorescein angiography, and OCT were performed before intervention and after 4 months. Quantitative measurement of angiographic variables such as the amount of hard exudates (HE), size of foveal avascular zone (FAZ), and leakage severity was performed by computer, using Photoshop software. RESULTS: Initial best-corrected visual acuity (VA) was 0.93+/-0.39 logMAR in the placebo group and 0.75+/-0.38 logMAR in the treatment group. At 4 months, corrected VA was 0.88+/-0.48 logMAR in the controls versus 0.71+/-0.42 logMAR in the cases. Mean central macular thickness measured by OCT before and 4 months after injection was 392 and 377 microns in the treatment group and 388 and 357 microns in the placebo group, respectively. No statistically significant difference was detected between the two groups. The difference was also not significant in HE, FAZ, and leakage in the angiograms. CONCLUSIONS: Two injections of posterior sub-tenon TA had no therapeutic effect on refractory DME.

Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial.

AIMS: To evaluate the effect of tranexamic acid on early postvitrectomy haemorrhage in diabetic patients. METHODS: In a clinical trial, 62 diabetic patients scheduled for vitrectomy were randomly assigned to two groups. The treatment group (32 eyes) received two doses of tranexamic acid (10 mg/kg) shortly before and after the operation intravenously, continued orally for 4 days (20 mg/kg/8 hours). The control group (30 eyes) received no medication. Both media clarity and visual acuity were compared during 4 weeks. RESULTS: Four weeks after surgery visual acuity was low (< or =1 metre counting fingers) in 21.4%, moderate (>1 metre counting fingers but<20/200) in 14.3%, and good (> or =20/200) in 64.3% of the treated group. Corresponding figures in the control group were 26.1%, 26.1%, and 47.8%, respectively. These differences were of no statistical significance. The ratio of mild to severe vitreous haemorrhage during the first 4 days and after 4 weeks was 79% to 21% and 82% to 18% in the treatment group and 76.7% to 23.3% and 78.3% to 21.7% in the control group respectively, which showed no statistically significant difference. CONCLUSION: Tranexamic acid, with the method of administration in this study, had no effect on reducing early postvitrectomy haemorrhage in diabetic patients.

Therapeutic effects of laser photocoagulation and/or vitrectomy in Eales' disease.

PURPOSE: To determine visual outcomes and regression of retinal neovascularization following laser photocoagulation and/or vitrectomy in eyes with Eales' disease. METHODS: In a retrospective noncomparative study, the authors reviewed the existing data of 67 eyes of 54 patients with a diagnosis of Eales' disease who had undergone laser photocoagulation and/or vitrectomy based on their clinical presentations. Main outcome measures were visual acuity changes and regression of retinal neovascularization of the eyes following treatment. RESULTS: Both laser therapy and vitrectomy improved visual acuity and induced regression of retinal neovascularization. Forty-three eyes had undergone laser therapy; their rate of visual acuity 320/30 improved from 53% before treatment to 60% after treatment. Twenty-four eyes had undergone vitrectomy; rate of visual acuity 320/30 improved from 13% before surgery to 38% after surgery. In eyes that had undergone laser therapy, additional laser therapy controlled recurrent neovascularization in 47% of the eyes, but ultimately, 12% of them required vitrectomy. In the primary vitrectomized group, additional required treatment was repeat vitrectomy in 21%, and/or laser therapy in 29% of the eyes. CONCLUSIONS: Although laser photocoagulation should be the first line of treatment in Eales' disease, it cannot always induce regression of retinal neovascularization. In such cases vitrectomy may further enhance therapeutic success.

Outcomes of surgical (pars plicata and limbal lensectomy, vitrectomy) and non-surgical management of persistent fetal vasculature (PFV): an analysis of 54 eyes.

PURPOSE: To identify clinical characteristics associated with outcomes of treatment for persistent fetal vasculature (PFV based on a modified classification. METHODS: In this noncomparative case series, 54 eyes of 47 consecutive patients with PFV managed from 1981 until 1998 at a tertiary eye hospital were reviewed. Pars plicata lensectomy and vitrectomy was performed in 34 eyes and translimbal lensectomy and vitrectomy in five. Fifteen eyes were managed non-surgically. The following outcomes were measured: 1) "Visual improvement", defined as at least one Zipf's category improvement of best corrected final vision as compared with initial visual acuity, provided that final vision of CSUM (central, steady, unmaintained) equal to 20/100-20/30 was obtained. 2) "Cosmetic acceptability", defined as the absence of the following: small orbit, externally small appearing eye with microcornea and hypotony, eye deviation more than 35 prism diopters without strabismus surgery and corneal opacity. RESULTS: Six eyes were inoperable. In 10 out of 33 operated eyes (30.3%) improvement of vision was obtained including four eyes with an anterior form and six eyes with a combined form of PFV. In univariate analysis, factors such as anterior form of PFV surgery in the combined form and having a normal retina, had a weak association with a higher chance of visual improvement. In multivariate regression analysis the likelihood of unacceptable cosmetic appearance was higher in females than males (OR = 10.5), and in bilateral cases (OR = 7.9). Offspring of consanguineous marriages had more severe forms of PFV. CONCLUSIONS: Although visual potential is limited in PFV some eyes with an anterior or combined form and normal retina achieved improvement of visual acuity after surgery. However, statistically no single factor except sex and bilateral PFV (for cosmetic unacceptability) reliably predicted the results of treatment. Therapy should be individualized based on clinical findings. Genetic studies in offspring of consanguineous marriages with PFV may prove informative.

Intra-ocular lens implantation in children.

Intra-ocular lens (IOL) implantation in a growing eye of a young child brings several problems unique to this age group. Better understanding of the rate of refractive growth in children's pseudophakic eyes may help predicting future refractions in these eyes more accurately. Opacification of the posterior capsule, if remained intact, interferes with visual rehabilitation in children. Primary posterior capsulectomy and anterior vitrectomy provides the clarity of visual axis. Optical rehabilitation of children with unilateral aphakia is usually problematic. Posterior chamber IOLs are preferred to anterior-chamber IOLs for secondary implantation. In the absence of adequate capsular support and contact lens intolerance, a scleral-fixated IOL can be implanted. Scleral fixation of a posterior chamber IOL has encouraging short-term results but the long-term risks are not known yet. Intra-ocular lens implantation in infants is associated with major complications and is not recommended at present. The occurrence of open angle glaucoma is a sight-threatening late complication of pediatric cataract surgery. Intra-ocular lens implantation plays a protective role against aphakic glaucoma in children.

Factors influencing anatomic and visual results in primary scleral buckling.

PURPOSE: To identify the factors influencing anatomical and visual results in cases of rhegmatogenous retinal detachment undergoing primary scleral buckling. METHODS: A retrospective study of 233 eyes of 226 patients was done. The data were evaluated by univariate analysis and stepwise logistic regression analysis. RESULTS: Retinal reattachment was achieved with primary scleral buckling in 197 eyes (84.5%). The extent of retinal detachment, preoperative proliferative vitreoretinopathy (PVR), preoperative visual acuity and relative afferent pupillary defects were identified as influencing anatomical results, by univariate analysis. The predictive roles of extent of retinal detachment (P<0.0001) and preoperative PVR (P=0.0085) were shown to be significant by step-wise logistic regression. As well as the above factors, the patient's age, the duration of symptoms and the status of the macula were predictors of visual results, by univariate analysis. Stepwise logistic regression analysis confirmed the predictive roles of preoperative visual acuity (P<0.0001) and the extent of retinal detachment (P=0.0089). CONCLUSIONS: Cases with a larger extent of retinal detachment, more advanced preoperative PVR and poorer preoperative visual acuity have less favorable anatomical and functional results.

Primary capsulectomy, anterior vitrectomy, lensectomy, and posterior chamber lens implantation in children: limbal versus pars plana.

PURPOSE: To compare the results of a limbal versus a pars plana approach for primary posterior capsulectomy and anterior vitrectomy in the management of childhood cataract. SETTING: Department of Ophthalmology, Labbafinejad Medical Center, Tehran, Iran. METHODS: A randomized, controlled, double-masked clinical trial of 45 eyes was conducted. After being matched, 38 eyes were included in the study and were divided into 2 equal groups for data analysis. All eyes had lensectomy and posterior chamber intraocular lens (PC IOL) implantation. Primary posterior capsulectomy and anterior vitrectomy were performed through the limbus in half of the eyes and the pars plana in the other half. Main outcome measures included visual acuity, estimated red reflex, postsurgical inflammatory reaction, corneal clarity, posterior synechias, iris capture, IOL position, capsulectomy size, glaucoma, cystoid macular edema, retinal tear, and postoperative refraction. RESULTS: No statistically significant differences were found between the 2 approaches in the outcome measures. CONCLUSION: The anatomic and visual results were encouraging when posterior capsulectomy and anterior vitrectomy, using a limbal or pars plana approach, were combined with lensectomy and PC IOL implantation in children. The application of these techniques depends on surgeon experience and skill.

Surgical management of cataract and posterior chamber intraocular lens implantation in Fuchs' heterochromic iridocyclitis.

BACKGROUND: To determine the inflammatory course and level of visual rehabilitation after cataract extraction and posterior chamber lens implantation in patients with Fuchs' heterochromic iridocyclitis complicated by cataract. METHODS: In a clinical trial, 32 eyes (visual acuity of 20/160 or worse) of 30 patients underwent extracapsular cataract extraction (19 eyes) or lensectomy (13 eyes) accompanied by posterior chamber intraocular lens implantation. Indirect ophthalmoscopy was performed intraoperatively prior to intraocular lens implantation and the extent of vitreous haze was assessed. If vitreous haziness was 3+ or more, core vitrectomy (two eyes) or three-port pars plana deep vitrectomy (four eyes) was performed. RESULTS: After an average follow up of 14.4 months (6 to 24 months), there was no statistically significant increase in cell and flare in the anterior chamber and vitreous or in keratic precipitates compared with the preoperative status of the eyes. However, 12% of the eyes developed synechiae (anterior and/or posterior) in comparison to preoperative condition (p < 0.05). Eight-seven percent of the eyes gained visual acuity of 20/40 or better (P < 0.005). Using the logistic regression model, a higher level of preoperative inflammation was associated with reduced likelihood of gaining visual acuity of 20/25 or more (OR = 0.25, 95% CI 0.049, 1.255). The complications of surgery were synechiae, 12%; opaque posterior capsule, 12%; vitreous loss, 3%; chronic glaucoma, 3%; and retinal detachment, 3%. CONCLUSIONS: Implantation of a posterior chamber intraocular lens can be well tolerated in patients with Fuchs' heterochromic iridocyclitis. Vitrectomy, whenever indicated in addition to cataract extraction, improves visual rehabilitation.

Posterior segment triple surgery after traumatic eye injuries.

Cataract extraction, posterior chamber intraocular lens (PC-IOL) implantation, and complete vitrectomy combined in a one-stage procedure were performed in 16 eyes (16 patients) with traumatic eye injuries undergoing anterior lensectomy (seven eyes), extracapsular cataract extraction (six eyes), or pars plana lensectomy (three eyes). Membrane peeling and intraocular foreign-body removal (13 eyes, 6 with intraretinal foreign bodies) were performed as needed. Surgery was performed from 1 week to 10 years after injury. After an average follow up of 8 months, 13 eyes (81%) had a visual acuity of at least 20/200; 50%, at least 20/40.

Temporary keratoprosthesis for surgical management of complicated combined anterior and posterior segment injuries to the eye: combat- versus noncombat-injury cases.

We used a Landers-Foulks temporary keratoprosthesis lens to combine penetrating keratoplasty with vitreoretinal surgery in 21 eyes of 21 patients. Ten of these patients were victims of combat injuries; 11 had traumatic injuries unrelated to war. After a mean follow up of 11 months, satisfactory overall results, ie, an attached retina and a clear cornea, were obtained in nine eyes (42.8%). In two, the retina was attached but the corneal graft was rejected. Eight eyes achieved a visual acuity of 5/200 or better. The visual prognosis as well as the rate of retinal reattachment for the combat-injured eyes were poorer than those for the traumatic noncombat-injured eyes. At the last follow-up examination, 60% of the combat-injured eyes were considered visually lost, as compared with 36.3% of the noncombat-injured eyes.

Bilateral simultaneous optic neuritis in childhood systemic lupus erythematosus. A case report.

The authors describe an 11-year-old girl with systemic lupus erythematosus (SLE) who developed simultaneous bilateral acute optic neuritis. Severe initial visual loss followed by permanent visual deficit occurred in both eyes despite therapeutic intervention. Recurrence of optic neuritis in one eye caused the vision to deteriorate further. The most probable pathogenesis is occlusive vasculitis involving the small arterioles of the optic nerves.

Low dose cyclosporin-A therapy in Behçet's disease.

The effect of systemic low dose cyclosporin-A (5 mg/kg/day as initial dose) combined with 0.2 to 0.6 mg/kg/day prednisolone (when necessary) in clinical course of 22 patients suffering from severe forms of Behçet's disease are reviewed. All the patients had received other drugs previously and had either no response to them or developed intolerable side effects, therefore, pre treatment visual acuity (VA) was compared to post treatment VA as "self control". The average age of our patients was 30.6 years (range 19-51 years). The average duration of our therapy was 19.5 months (range 4-32 months). Improvement or stabilization of vision was achieved in 21 patients (95%). The intraocular inflammation was controlled in all of the eyes and most of the non-ocular signs and symptoms were also improved. Serious side effects included rise in creatinine in 10 (45%) of the patients, rise in bilirubin in 6 (27%) and hypertension in 1 (4.5%). These side effects disappeared as the dose of cyclosporin-A was tapered. We believe this form of therapy is of great value in the management of severe forms of Behçet's disease.

Surgical management of intraretinal foreign bodies.

PURPOSE: To identify the clinical features in eyes with intraretinal foreign bodies (IRFBs) and evaluate the results of surgical management in these cases. METHODS: The records of 75 patients (76 eyes) with IRFBs were retrospectively reviewed. All eyes underwent vitrectomy. The IRFBs were removed with intraocular forceps in 45 eyes (59.2%) and by magnetic extraction in 31 eyes (40.8%), either through pars plana sclerotomy or through the sclera over the IRFB after precise localization. Laser photocoagulation or cryotherapy was performed around the IRFB before surgery in 38 eyes. RESULTS: The average follow-up period was 34 months. Of the 75 patients, 46 (61.3%) were injured at war. The IRFBs were metallic in 71 (93.4%) eyes. Of these, 59 (83%) were ferromagnetic. In these 76 eyes, final visual acuity was 20/15-20/40 in 37 (48.6%), and 20/50-20/200 in another 10 (13%). In 19 eyes (25%), partial or total retinal detachment was present at the final follow-up examination. CONCLUSION: Surgical management of IRFBs is a complicated procedure. The appropriate route of removal may be determined by the type and site of the embedded IRFB. Performance of a meticulous vitrectomy is mandatory, and an attempt should be made to minimize the rate of iatrogenic peripleral retinal breaks. Preoperative retinopexy around the site of the embedded foreign body is recommended, if possible, to reduce the risk of retinal detachment. The prognosis in eyes with IRFBs and rhegmatogenous retinal detachment is guarded.

Vitrectomy in ocular trauma. Factors influencing final visual outcome.

The results of vitrectomy in 240 consecutive cases of ocular trauma were reviewed. Of these cases, 71.2% were war injuries. Intraocular foreign bodies were present in 155 eyes, of which 74.8% were metallic and 61.9% ferromagnetic. Multivariate analysis identified the prognostic factors predictive of poor visual outcome, which included: (1) presence of an afferent pupillary defect; (2) double perforating injuries; and (3) presence of intraocular foreign bodies. Association of vitreous hemorrhage with intraocular foreign bodies was predictive of a poor prognosis. Eyes with foreign bodies retained in the anterior segment and vitreous had a better prognosis than those with foreign bodies embedded in the retina. Timing of vitrectomy and type of trauma had no significant effect on the final visual results. Prophylactic scleral buckling reduced the incidence of retinal detachment after surgery. Injuries confined to the cornea had a better prognosis than scleral injuries.

Association of herpetic encephalitis with acute retinal necrosis syndrome.

Bilateral acute retinal necrosis syndrome developed shortly after a severe acute encephalitis in two previously healthy adults. The clinical and laboratory data suggested that herpes simplex virus was the cause of the encephalitis and acute retinal necrosis in these patients. To the authors' knowledge, this is the first report of an association of herpetic encephalitis with acute retinal necrosis in the literature.