Rehan M. Hussain

RANIBIZUMAB FOR DIABETIC MACULAR EDEMA REFRACTORY TO MULTIPLE PRIOR TREATMENTS

Purpose: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. Methods: Retrospective chart review. Results: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 &mgr;m. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 &mgr;m. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. Conclusion: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab.

UV-independent p53 mutations in sebaceous carcinoma of the eyelid.

Purpose: Sebaceous carcinoma of the eyelid is a potentially fatal malignancy that has been associated with p53 gene mutations. The purpose of this study is to determine the frequency of p53 mutations in sebaceous carcinoma of the eyelid and to determine whether there is any relationship between the presence of p53 mutations and tumor invasiveness. Methods: Retrospective case series. Fourteen samples of sebaceous carcinoma that had been resected from Caucasian patients between 1994 and 2010 were analyzed for p53 gene mutations with PCR and Sequencher software. Patient charts were reviewed to draw clinicopathologic correlations in relation with the presence of p53 gene mutations. Results: Seven of 14 (50%) sebaceous carcinoma samples were found to have p53 gene mutations. None of the samples had tandem mutations, which are caused by UV exposure. No statistically significant trend was found between the presence of p53 mutations and metastasis, recurrence, tumor size, TNM stage, and pagetoid spread. There was a similar frequency of p53 gene mutations found in stage T1, T2, and T3 tumors. Conclusions: p53 Mutations are found in a high percentage of sebaceous carcinomas in the Caucasian population. The absence of tandem mutations is consistent with the belief that sebaceous carcinoma develops as a UV-independent process. There does not appear to be a significant correlation between the presence of p53 mutations and tumor size, recurrence, metastasis, pagetoid spread, or location. The similar frequency of p53 mutations in both low- and high-stage tumors implies that p53 gene mutations may be involved in early stages of carcinogenesis of sebaceous carcinoma.

Toxic anterior segment syndrome: Inadvertent administration of intracameral lidocaine 1% and phenylephrine 2.5% preserved with 10% benzalkonium chloride during cataract surgery

Purpose: To report 3 patients with corneal decompensation and anterior uveitis within 24 hours of cataract surgery from a single ambulatory surgery center using intracameral lidocaine HCl 1% and phenylephrine 2.5% inadvertently preserved with 10% benzalkonium chloride. Methods: This case series describes 3 patients who underwent traditional cataract extraction with a significant decrease in visual acuity in the immediate postoperative period resulting in secondary surgical intervention for corneal decompensation in 2 patients. Results: All 3 patients experienced a dramatic decrease in visual acuity on the day of surgery, ranging from 20/400 to light perception. They were treated with topical steroids and sodium chloride, with stabilization of vision at 20/60 in 1 patient. The remaining 2 patients did not recover with medical management. One underwent Descemet stripping automated endothelial keratoplasty with placement of the corneal graft on top of Descemet membrane, which could not be removed secondary to extensive fibrosis. The third patient underwent penetrating keratoplasty secondary to deep corneal scarring. Conclusions: This is the first case series of toxic anterior segment syndrome occurring secondary to the use of benzalkonium chloride-preserved intracameral lidocaine and phenylephrine. Clinicians should remain alert to this phenomenon, and should refrain from using intracameral preservatives during cataract surgery.

Unusually delayed presentation of persistent Descemet's membrane tear and detachment after cataract surgery

A 51-year-old male who had undergone phacoemulsification in his left eye 11 months prior presented with complaint of sudden onset of blurred vision in the same eye. Review of his clinical course, slit-lamp exam, pachymetry, and specular endothelial microscopy led to the diagnosis of acute hydrops caused by Descemet’s membrane dehiscence at the site of the incision. He was initially managed with medical treatment and observation. In the subsequent months of follow-up, the corneal edema and the patient’s visual acuity did not improve. Intracameral gas injection was performed 7 months after presentation, but because of persistent corneal edema and nonattached Descemet’s membrane, penetrating keratoplasty was performed. Histopathologic examination confirmed the diagnosis. The patient has had a clear corneal graft since then. Although Descemet’s membrane detachment is a rather common complication after intraocular surgery, its unusually delayed presentation can also occur, and should not be confused with pseudophakic bullous keratopathy. Many mechanisms have been studied for the development of early tears and detachments after cataract surgery, but little is known about late presentations. The authors explore possible causes, and highlight the importance of instructing patients to avoid eye rubbing and any other type of trauma to the cornea after intraocular surgery.

Pharmacotherapy of retinal disease with visual cycle modulators

ABSTRACT Introduction: Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies. Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

Epithelial Downgrowth in the Vitreous Cavity and on the Retina in Enucleated Specimens and in Eyes with Visual Potential

Purpose: To report clinical course and visual and anatomical outcomes of six eyes with histopathologically confirmed vitreous cavity and retina epithelial downgrowth. Methods: This is a retrospective 15-year review of archived pathologic slides and corresponding medical records of patients with vitreous cavity and retina epithelial downgrowth. Posterior segment epithelial downgrowth was defined as epithelial or goblet cells in the vitreous cavity or on the surface of the retina. Results: Histopathologic diagnosis of epithelial downgrowth was made in 122 patients. Of those, 6 patients (5%) had vitreous cavity and retina epithelial downgrowth. Three patients developed blind painful eye, and epithelial downgrowth was identified in enucleated specimens. The other three eyes with visual potential presented with tractional retinal detachments. Epithelial downgrowth was identified in epiretinal membranes obtained during pars plana vitrectomy. The latter group had more previous surgeries (P = 0.03), and all had keratoprosthesis implantation as their last surgery. All three had pathologic specimens obtained at the time of the keratoprosthesis implantation; no anterior segment epithelial downgrowth was noted in two patients, and one patient had involvement of corneal button, iris, and posterior capsule. Final visual acuity ranged from hand motion to light perception. Conclusion: In the current study, vitreous cavity and retina epithelial downgrowth occurred after multiple intraocular surgeries, including repair of the open globe injuries both in enucleated specimens and in eyes with visual potential. In eyes with visual potential, keratoprosthesis implantation seems to predispose the development of posterior segment epithelial downgrowth.

Stargardt macular dystrophy and evolving therapies

ABSTRACT Introduction: Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments. Areas covered: Investigational therapies for STGD1 aim to reduce toxic bisretinoids and lipofuscin in the retina and retinal pigment epithelium (RPE). These agents include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Avacincaptad pegol is a C5 complement inhibitor that may reduce inflammation-related RPE damage. Animal models of STGD1 show promising data for these treatments, though proof of efficacy in humans is lacking. Fenretinide and emixustat are VCMs for dry AMD and STGD1 that failed to halt geographic atrophy progression or improve vision in trials for AMD. A1120 prevents retinol transport into RPE and may spare side effects typically seen with VCMs (nyctalopia and chromatopsia). Stem cell transplantation suggests potential biologic plausibility in a phase I/II trial. Gene therapy aims to augment the mutated ABCA4 gene, though results of a phase I/II trial are pending. Expert opinion: Stem cell transplantation, ABCA4 gene therapy, VCMs, and complement inhibitors offer biologically plausible treatment mechanisms for treatment of STGD1. Further trials are warranted to assess efficacy and safety in humans.

EFFICACY OF DEXAMETHASONE INTRAVITREAL IMPLANT FOR REFRACTORY MACULAR EDEMA CAUSED BY RETINAL VEIN OCCLUSION.

Purpose: To investigate efficacy of dexamethasone intravitreal (DEX) implant in treating refractory macular edema caused by retinal vein occlusion. Methods: Retrospective chart review. Results: Twenty-two eyes with refractory macular edema caused by retinal vein occlusion were treated with a mean of 2.2 DEX over 12 months. Patient had previously received a mean of 7 treatments (laser, bevacizumab, and/or triamcinolone) for macular edema present for at least 4 months duration (mean 20.8 ± 17.6 months, range 4–72 months) before starting DEX. Mean baseline visual acuity was 20/91, and mean central subfield thickness was 506 &mgr;m. DEX improved mean best-corrected visual acuity to 20/75 and 20/66 at 7 weeks and 6 months follow-up, although it worsened to 20/132 at 12 months. Mean central subfield thickness improved to 292, 352, and 356 &mgr;m at 7 weeks, 6 months, and 12 months follow-up, respectively. There was a statistically significant association between number of DEX treatments and central subfield thickness (P = 3.28 × 10−9). There was a statistically significant association between number of days followed and best-corrected visual acuity (P = 0.006). Six of 12 (50%) phakic patients developed visually significant cataract requiring surgery. Five of 22 (23%) patients developed ocular hypertension (intraocular pressure > 30) and consequently did not undergo further treatment with DEX. Conclusion: DEX resulted in sustained anatomical reduction of retinal vein occlusion–associated refractory macular edema, although this did not translate into long-term best-corrected visual acuity improvement in either phakic or pseudophakic patients, possibly related to chronic structural alterations in the retina despite reduction of edema.

Recurrent orbital adult-type fibrosarcoma in a 3-year-old girl

A 3-year-old Filipino girl presented with progressive left-sided ptosis and proptosis after resection of a superomedial orbital tumor 2.5 years ago. She had been followed with serial MRI, which demonstrated interval growth of a recurrent lesion. Repeat resection was undertaken via an eyelid-splitting anterior orbitotomy. The patients pediatric oncologist and sarcoma specialist did not recommend adjuvant chemotherapy, and the family declined proton radiotherapy. The patient will continue to be monitored with serial imaging. Histopathology, immunohistochemistry, and reverse transcriptase polymerase chain reaction were most consistent with a diagnosis of adult-type fibrosarcoma. This is the first reported case of adult-type fibrosarcoma presenting in the orbit of a child. Fibrosarcoma is a fibroblast-derived tumor that commonly presents in the extremities, usually in patients in their fourth to sixth decades. It is rarely seen in the orbit, with the largest case series to date only including 5 patients.

In Vivo Effects of Femtosecond Laser–Assisted Keratoplasty

IMPORTANCE The femtosecond laser is reported to cut lamellar surfaces with varying degrees of smoothness depending on the depth of the cut, with deeper cuts leaving less smooth surfaces. We attempted to evaluate the smoothness of the deeper lamellar surface as cut by the femtosecond laser after allowing 3 months of in vivo healing. OBSERVATIONS Two patients underwent penetrating keratoplasty 3 months after inadequate visual rehabilitation following femtosecond laser-assisted sutureless anterior lamellar keratoplasty for the treatment of anterior stromal scars. In vivo confocal microscopy that was performed before penetrating keratoplasty demonstrated an acellular zone with a hyperintense signal consistent with a mild interface opacification. Light microscopy in one patient demonstrated scarring limited primarily to the posterior stroma; in the other patient, the interface was smooth with mild scarring of the anterior lamellae. When studied with electron microscopy, the cut surfaces revealed a smooth to very mild stuccolike appearance that was smoother than anticipated. CONCLUSIONS AND RELEVANCE After 3 months of in vivo healing, the lamellar interface produced by the femtosecond laser, as imaged by electron microscopy, appeared to be nearly smooth with minimal roughness to the cut surfaces. We attribute this to the effects of in vivo healing and remodeling.