Nisha V Shah

Combination therapy with triamcinolone acetonide and bevacizumab for the treatment of severe radiation maculopathy in patients with posterior uveal melanoma

Purpose To evaluate the role of intravitreal triamcinolone acetonide in patients who developed severe, visually compromising radiation maculopathy or progressed despite anti-angiogenic treatments. Methods An Institutional Review Board approved, consecutive, retrospective study from 2006 to 2009 of patients who developed severe, visually compromising radiation retinopathy manifesting as macular edema secondary to iodine-125 plaque brachytherapy for posterior uveal melanoma, were treated with a combination of intravitreal bevacizumab and intravitreal triamcinolone. Patients were evaluated with spectral domain optical coherence tomography (SD-OCT) at 2–4 month intervals following plaque removal. Treatment with intravitreal bevacizumab commenced at the first signs of visually compromising macular edema diagnosed with SD-OCT. Triamcinolone acetonide was administered to patients with severe maculopathy as consolidative therapy, or for patients that were refractory to repeated bevacizumab injections with persistent or worsening cystoid macular edema and lack of improvement or progressive worsening of best corrected visual acuity (BCVA). Results Twenty-five patients were evaluated after receiving a combination of intravitreal bevacizumab and triamcinolone. Initial treatment commenced at a mean of 14.5 (range of 2–42) months after plaque brachytherapy. Patients were given a mean of two injections (range 1–6) of triamcinolone acetonide, and a mean of 8.8 bevacizumab injections (range of 1–26) with a mean follow-up of 31.2 months. Radiation maculopathy upon first detection had a mean SD-OCT grade of 3.6 (median = 4), with an associated mean entry level BCVA of 20/70. Visual acuity at time of first intravitreal triamcinolone was 20/138. At last follow-up (mean of 45.5 months after plaque brachytherapy) mean BCVA was 20/136; however, 9 of 25 (36%) patients who presented with severe radiation maculopathy demonstrated 20/50 or better vision at last follow-up. Conclusion This case series suggests a beneficial role for intravitreal triamcinolone as a consolidation treatment for patients who present with severe radiation maculopathy or as an adjuvant to bevacizumab for refractory or progressive maculopathy.

Early SD-OCT diagnosis followed by prompt treatment of radiation maculopathy using intravitreal bevacizumab maintains functional visual acuity

Purpose: To evaluate the benefits of intravitreal bevacizumab in patients with visually compromising radiation maculopathy following iodine-125 plaque brachytherapy for uveal melanoma. Methods: In this Institutional Review Board-approved, consecutive, retrospective study from 2006–2009 of patients maintaining 20/50 or better vision following treatment for visually compromising radiation maculopathy, patients were evaluated with spectral domain optical coherence tomography at 2–4 month intervals following plaque removal. Treatment with intra-vitreal bevacizumab commenced at the first signs of radiation vasculopathy on spectral domain optical coherence tomography with associated decreased best corrected visual acuity, followed by repeat injections for recurrent or persistent vasculopathic changes. Results: At 3 years following plaque brachytherapy, 81 of 159 (50.9%) patients treated for radiation maculopathy demonstrated 20/50 or better vision at median follow up of 36 months, which demonstrates significant improvement in vision as compared to the Collaborative Ocular Melanoma Study (P < 0.0001). These 81 patients were given a mean of five injections (range 1–17) over a mean of 17.6 months (range 1–54 months), starting at 15.8 months (range 3–50 months) after plaque brachytherapy. For those eyes that maintained 20/50 or better vision at the final follow-up, pretreatment mean best corrected visual acuity of 20/43 improved to 20/31. Conclusion: This study demonstrates that spectral domain optical coherence tomography can detect early vasculopathic changes secondary to radiation maculopathy and that prompt treatment with intravitreal bevacizumab may delay vision loss and maintain or possibly improve visual acuity in half of eyes diagnosed with radiation maculopathy. Radiation maculopathy remains a therapeutically manageable morbidity associated with radiation therapy for posterior uveal melanoma.

Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detachment.

Background The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma. Methods This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity. Results One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40). Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40) at 4 months, with stabilization to 20/57 (median 20/40) at 8 months, 20/56 (median 20/30) at 12 months, and 20/68 (median 20/50) at 24 months. Tumor volume following combined therapy was shown to be reduced by 22.2% at 3 months, 28.9% at 6 months, 39.3% at 12 months, and 52.2% at 24 months (all P < 0.001). All patients tolerated the procedure well without systemic side effects. Conclusion Intravitreal bevacizumab may be used as an adjuvant agent following plaque brachytherapy. Treated choroidal melanomas show reduction in tumor volume as well as resolution of exudative retinal detachments.

Evaluation of the surgical learning curve for I-125 episcleral plaque placement for the treatment of posterior uveal melanoma: a two decade review.

Purpose To evaluate the surgical learning curve in episceral plaque brachytherapy placement in the management of posterior uveal melanoma. Methods A retrospective chart review of two cohorts of 250 consecutive patients undergoing plaque placement for posterior uveal melanoma from 2002 to 2004 and from 2008 to 2009 was conducted. The plaque–tumor apposition rates verified by intraoperative echography were evaluated and correlated with surgical volume over a 19-year period. Results In an initial study of 29 consecutive patients undergoing plaque placement from January 1992 to January 1995, a suboptimal plaque placement rate of 21% (n = 29) was identified. This percentage declined to 12% (n = 100) from January 2002 to January 2004, and further declined to 4% (n = 150) from June 2008 to August 2009. The tumor–plaque apposition rates for these three groups were 79% (1992–1995), 88% (2002–2004), and 96% (2008–2009). An estimated surgical volume of 1275 cases was performed to achieve a >90% precision rate for first application of primary plaque centration. Conclusion There are challenges to mastering the precise placement of radioactive plaques for posterior uveal melanoma. We have demonstrated a significant learning curve for plaque placement techniques, and have emphasized the importance of intraoperative ultrasound in the verification of plaque placement, thus allowing for intraoperative repositioning.

Femtosecond laser-assisted retreatment for residual refractive errors after laser in situ keratomileusis

Purpose To study the utility of creating an additional side cut within the old laser in situ keratomileusis (LASIK) flap using a femtosecond laser to reduce the incidence of epithelial ingrowth in patients having retreatments for residual refractive errors after LASIK. Setting Bascom Palmer Eye Institute, Miller School of Medicine, Miami, Florida, USA. Design Comparative case series. Methods On a chart review of all cases that had retreatment between January 2004 and April 2011, eyes in which an additional side cut with the femtosecond laser within the old LASIK flap margin was created were classified as Group 1. All eyes having retreatment using traditional flap‐relifting techniques between January 2008 and April 2011 were classified as Group 2. Results Twenty‐four eyes of 18 patients had femtosecond laser–assisted retreatment with side cut only (Group 1), while 103 eyes of 80 patients had a flap‐lift LASIK enhancement (Group 2). Twenty‐seven cases of epithelial ingrowth were identified in the 2 groups, 4 cases (17%) in the side‐cut group and 23 cases (22%) in the flap‐lift group. There was a statistically significant difference between the 2 groups in the incidence of epithelial ingrowth in patients in which the microkeratome was used as the initial method of flap creation (P<.05). Conclusion Femtosecond laser–assisted side‐cut LASIK resulted in a statistically significant lower incidence of epithelial ingrowth after stratification because of the higher risk for epithelial ingrowth in patients who had primary LASIK with microkeratome flaps. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Infectious Pseudomonas and Bipolaris scleritis following history of pterygium surgery

We report an interesting case of infectious scleritis from coinfection of Pseudomonas aeruginosa and Bipolaris with no corneal infiltrate. A healthy 60-year-old man with a history of infectious scleritis following pterygium excision presented with purulent material growing P. aeruginosa and 1+ colonies of Bipolaris species of fungus. Broad spectrum treatment was initiated with hourly topical moxifloxacin, fortified tobramycin, and natamycin along with a subconjunctival injection of voriconazole and topical cyclosporine, with PO ketoconazole. After 10 weeks of aggressive empiric treatment, the patients symptoms had resolved, and his vision returned to baseline although a scleral patch graft was utilized to stabilize scleral thinning.

Treatment of vascular activity secondary to atypical choroidal nevus using intravitreal bevacizumab.

Objective To report the optical coherence tomography (OCT) findings of 27 eyes treated with intravitreal bevacizumab for intraretinal and subretinal vascular activity associated with atypical choroidal nevi. Methods This was an Internal Review Board-approved retrospective review of 27 eyes of 27 patients with choroidal nevus treated for secondary vascular activity with intravitreal injections of bevacizumab, performed by a single surgeon (TGM) at the Bascom Palmer Eye Institute. All patients were rigorously evaluated before the procedure and followed thereafter with ophthalmic examinations, refractive analysis, fundus photos, optical coherence tomography (OCT), and ocular echography. Patient demographics, tumor characteristics, dates of bevacizumab injections, and spectral-domain (SD)-OCT findings at each injection were recorded. Macular edema was graded as per SD-OCT findings for the initial and final visit. Results The mean age was 66.6 years (range, 40–86 years), with ten males and 17 females. Mean, median, and range baseline best corrected visual acuity (BCVA) were 20/53, 20/40, and 20/20–4/200, respectively. After a mean follow up of 29 months, the final BCVA mean, median, and range were 20/50, 20/40, and 20/20–20/400, respectively. The final BCVA ranged from 20/20 to 20/25 in nine eyes, while only six eyes had an initial BCVA within the same range. All patients demonstrated OCT findings of vascular activity suggestive of choroidal neovascularization (CNV). Initial SD-OCT findings included intraretinal cysts in eleven eyes, intraretinal fluid in six eyes, subretinal fluid in 14 eyes, pigment epithelial detachment in six eyes, epiretinal membrane in five eyes, and subretinal neovascularization in 14 eyes. On fundus photos, four eyes presented retinal hemorrhage. A mean of eight (range of 1–31) intravitreal bevacizumab (1.25 mg/0.05 cc) injections were given in all cases. A total of 37% (10/27) of eyes had complete or partial regression of vascular activity. The mean initial OCT classification for macular edema was 3 and a mean grade of 3 was maintained at the final follow-up OCT. All 27 choroidal nevi remained stable, and there were no adverse effects from the bevacizumab injections. Conclusion To our knowledge, this is the largest published case series of eyes treated with intravitreal bevacizumab for vascular activity associated with choroidal nevus. Intravitreal bevacizumab seems to be effective in the treatment of CNV secondary to choroidal nevus, and OCT can be a useful tool in the follow up of these patients, to assess the regression of CNV and to monitor macular edema.

Intraoperative Ultrasonography Aids Plaque Positioning

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Prospective, Double-masked, Randomized Trial Comparing Lidocaine Gel to Tetracaine Drops in Femtosecond Laser–assisted LASIK

Prospective, Double-masked, Randomized Trial Comparing Lidocaine Gel to Tetracaine Drops in Femtosecond Laser–assisted LASIK Despite the use of topical anesthetics, patients report intraand/or postoperative pain and discomfort during LASIK, particularly during fl ap creation and during the fi rst several hours after LASIK.1 Evidence suggests that gel preparations of topical anesthetics may be more effective than aqueous-based drops, due to their prolonged contact with the ocular surface and deeper penetration into the aqueous humor.2 In fact, a prior study in eyes undergoing LASIK with a microkeratome found decreased pain in the eye that received supplementary lidocaine 2% gel compared to the eye that received 0.5% proparacaine alone.3 We designed the fi rst study (to our knowledge) comparing the anesthetic effi cacy and surgical outcomes between lidocaine 2% gel and tetracaine 0.5% drops in patients undergoing bilateral femtosecond laser–assisted LASIK. This University of Miami, IRB-approved, prospective, single-center, randomized, double-masked, paired-eye comparison intended to include 80 eyes from 40 healthy adults not taking pain medications. However, the study was halted after 22 eyes from 11 patients were enrolled due to patient safety concerns (ie, when 1 patient developed irregular, thin fl ap in the eye receiving lidocaine 2% gel). A 0.25-inch application of 2% lidocaine gel was administered 10 minutes prior and again at 5 minutes prior to LASIK with a supplement of 0.5% tetracaine administered at time 0 in 1 eye, selected at random by a data allocation sheet. For the fellow eye, 2 drops of 0.5% tetracaine were given at 10 and 5 minutes prior to and at the time of LASIK. Main outcome measures included baseline and postoperative pain scores (1 indicating no pain and 4 indicating severe pain for 12 different pain descriptions) assessed immediately after and 1 hour following LASIK; uncorrected (UDVA) and corrected distance visual acuity (CDVA) measured at 1 day and 1 month postoperatively; and intended versus actual fl ap thickness. The study was in compliance with Good Clinical Practices, the Declaration of Helsinki (1996), Clinical Trials.gov (Trial# NCT01383200), and informed consent (US 21 CFR part 50) and HIPAA regulations. The study found no difference in visual acuity and showed similar pain levels between the treatment arms. However, we found that the femtosecond laser fl aps were signifi cantly thinner than intended in eyes that received lidocaine gel compared to those that received tetracaine drops. When comparing the intended fl ap thickness to the actual fl ap thickness, eyes receiving lidocaine gel were a mean of 10 22.71 μm thinner than intended, compared to the tetracaine drop eyes, which were 8.6 27.87 μm thicker (P=.04). These differences in fl ap difference may be related to the formation of a thin gel layer on the surface of the cornea, which can induce scatter and thus affect the precision of the femtosecond laser beam.4 Our fi nal patient developed an irregular, thin fl ap, likely caused by a remaining gel–cornea interface that affected the depth of the femtosecond laser beam (Fig). However, it may be possible to use a gel interface for therapeutic applications with the femtosecond laser in cases of irregular corneal surfaces. Furthermore, this study suggests that a small residual gel layer may remain following copious rinsing with balanced saline solution, reinforcing the practice that antiseptics for endophthalmitis prophylaxis prior to cataract surgery need to be administered prior to the gel anesthetic in patients undergoing cataract surgery. Thus, our study suggests that using anesthetic gel with the femtosecond laser for fl ap creation may not be the ideal alternative to tetracaine drops for femtosecond laser–assisted LASIK, due to the potential risk for fl ap complications.