Emilio Balestrazzi

Natural History of Macular Subretinal Hemorrhage in Age-Related Macular Degeneration

Purpose: To define the natural course of extensive submacular hemorrhage in age-related macular degeneration (AMD). Patients and Methods: The clinical charts of 54 patients (60 eyes) older than 55 years with subretinal hemorrhage larger than 1 disk diameter and extending beneath the fovea were retrospectively reviewed. The age of the patient, the use of antihypertensive or anticoagulant medication, visual acuity, biomicroscopic and fluorescein and indocyanine green (in 33 cases) angiographic data were recorded at presentation and during follow-up. Results: At the initial examination, average visual acuity was 20/240 (range from 20/70 to light perception). During follow-up (mean 24 months) visual acuity worsened in 80% of the eyes with a mean final visual acuity of 20/1,250 (range from 20/100 to light perception). The initial size and thickness of hemorrhage were correlated with initial and final visual acuity. Recurrence of hemorrhage resulted in an important impact on final visual acuity. Anatomic outcome showed fibrous tissue proliferation in 23 eyes (38.3%), atrophic scar in 15 eyes (25%) and occurrence of a retinal pigment epithelium tear in 13 eyes (21.6%). Conclusion: The visual outcome in eyes with submacular hemorrhages due to AMD is very poor. Size and thickness of the hemorrhage influenced negatively the natural prognosis. A surgical approach can be considered although it has not yet a widespread use.

Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia.

PURPOSE Epithelial hyperplasia is one of the factors that plays a role in myopic regression after photorefractive keratectomy (PRK). We evaluated the role of the epithelium following excimer laser in situ keratomileusis (LASIK) performed on highly myopic eyes. METHODS Fifty eyes of 32 patients (18 females and 14 males; mean age, 31.7+/-6.5 years) were treated with LASIK for myopia with an attempted correction ranging between -8.50 and -12.25 D (mean, -10.48+/-1.43 D). No sutures were placed. The thickness of the central epithelium was evaluated either with a 50-MHz ultrasonic pachymeter or an ultrasound biomicroscope. Postoperatively, topical corticosteroid drops were administered for at least 1 month. RESULTS Follow-up was at least 12 months. Epithelium measurements were thicker compared to preoperative measurements from the first week postoperatively (mean, +1.9 microm, +2.77%; P<.05). Epithelial thickness peaked at the third month after LASIK (mean, +6.5 microm, +9.5%; P<.05) and remained stable through 12 months. A negative correlation between epithelium thickness and manifest refraction from the first month postoperatively to the end of follow-up was present. CONCLUSION The epithelium seemed to have a role in the regression of refractive effect after LASIK to correct high myopia.

Local chemotherapy with interferon-α for conjunctival mucosa-associated lymphoid tissue lymphoma: A preliminary report1

OBJECTIVE To evaluate the efficacy of subconjunctival interferon-alpha for the treatment of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN Small, noncomparative, interventional case series. PARTICIPANTS Five patients with histologically proven conjunctival MALT lymphoma were studied prospectively. METHODS Patients were given 1,500,000 international units (IU) of interferon-alpha (IFN-alpha) (Roferon-A) subconjunctivally inside the lesion, three times a week for four weeks. If there was even a minimal response, a further cycle of 1,000,000 IU three times a week for four weeks was administered. Patients received a maintenance dose of 1 million IU, every 15 days for 4 times, after clinical resolution of the lesion. MAIN OUTCOME MEASURES Patients were followed clinically, with slit lamp examination, for evidence of tumor disappearance or recurrence. RESULTS Complete response was obtained in all patients. The lesion resolved completely by the eighth week. Four patients did not show any local recurrence with a median follow-up of 21 months (12-36 months). One patient presented with a recurrence after 11 months, in association with systemic lymphoma progression. CONCLUSIONS Local chemotherapy with IFN-alpha seems to be an effective treatment modality, alternative to radiotherapy, for conjunctival MALT lymphomas.

Comparison of corneal aberration changes after laser in situ keratomileusis performed with mechanical microkeratome and IntraLase femtosecond laser: 1-year follow-up.

Purpose: To compare corneal aberration changes 1 year after myopic laser in situ keratomileusis (LASIK) performed with a mechanical microkeratome and IntraLase femtosecond laser. Methods: Twenty four eyes of 15 patients underwent LASIK with the Hansatome microkeratome, and 23 eyes of 13 patients underwent LASIK with the IntraLase femtosecond laser. A standard ablation was performed with the Bausch & Lomb Technolas 217 excimer laser. Topography data were used to calculate corneal aberrations with a 3.0 mm and 5.00 mm pupil, before and 12 months after surgery. The increasing factor (IF), defined as the ratio between the postoperative and preoperative mean value of the optical aberration, was calculated. The method of Mulhern et al was used to evaluate the centration of ablation. The comalike aberration was correlated with the decentration of ablation. The Student t test was used for the statistical anaylsis. Results: The postoperative mean decentration of ablation was <0.5 mm. The comalike aberration appeared to be positively correlated with the decentration of ablation in both groups with a 5.0-mm pupil (P < 0.05). With a 3.00-mm pupil, the comalike aberration changed in the Hansatome group, whereas with a 5.00-mm pupil, all aberrations statistically significantly changed in both groups (P < 0.05). The IF similarly increased in 2 groups for spherical-like aberration, whereas IF greatly increased for total and comalike aberrations in the Hansatome group. Conclusions: Wavefront corneal aberrations change significantly 1 year after myopic LASIK performed with the Hansatome microkeratome as well as with IntraLase femtosecond lasers. Both of the procedures induce higher-order aberrations in the anterior corneal surface, but the amount of comalike aberration increases more with the Hansatome mechanical microkeratome.

Intravitreal bevacizumab (Avastin®) in proliferative diabetic retinopathy

Purpose:  To evaluate the efficacy and safety of intravitreal bevacizumab in proliferative diabetic retinopathy (PDR) patients.

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells

AIM Limbal cultures restore the corneal epithelium in patients with ocular burns. We investigated the biological parameters instrumental for their clinical success. METHODS We report a long-term multicenter prospective study on 152 patients carrying corneal destruction due to severe ocular burns, treated with autologous limbal cells cultured on fibrin and clinical-grade 3T3-J2 feeder cells. Clinical results were statistically evaluated both by parametric and nonparametric methods. RESULTS Clinical outcomes were scored as full success, partial success and failure in 66.05, 19.14 and 14.81% of eyes, respectively. The total number of clonogenic cells, colony size, growth rate and presence of conjunctival cells could not predict clinical results. Instead, the clinical data provided conclusive evidence that graft quality and likelihood of a successful outcome rely on an accurate evaluation of the number of stem cells detected before transplantation as holoclones expressing high levels of the p63 transcription factor. No adverse effects related to the feeder layer have been observed and the regenerated epithelium was completely devoid of any 3T3-J2 contamination. CONCLUSION Cultures of limbal stem cells can be safely used to successfully treat massive destruction of the human cornea. We emphasize the importance of a discipline for defining the suitability and the quality of cultured epithelial grafts, which are relevant to the future clinical use of any cultured cell type.

Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer

In mouse models of retinopathy of prematurity (ROP) inhibitors of vascular endothelial growth factor (VEGF) functions administered systemically completely block retinal neovascularization. In contrast, selective ocular VEGF depletion has achieved an approx. 50% inhibition of retinal neovascular growth. It is unclear whether a more complete inhibition of new blood vessel development can be obtained with an anti‐VEGF therapy localized to the eye. Therefore, the objective of the present study was to determine the effect of local anti‐VEGF therapy in a different animal model which closely mimics human ROP.

Unilateral amblyopia: An optical coherence tomography study

PURPOSE To determine whether retinal nerve fiber layer thickness (RNFLT), macular thickness (MT), and foveal volume (FV) in patients with unilateral amblyopia differ between the amblyopic and the sound eye. METHODS A Humphrey-Zeiss Stratus (OCT3) with software 4.0.3.1 was used to evaluate 40 patients (17 male, 23 female; mean age, 15.2 years; range, 5-56 years) with unilateral amblyopia. Patients were divided into 2 groups: 20 strabismic and 20 anisometropic. Maps of macular thickness and RNFL thickness (3.46) created by the use of optical coherence tomography were applied to calculate FV and MT and RNFLT. RESULTS Mean best-corrected visual acuity was +0.3 LogMAR (range, +0.2 to +1.0) in the amblyopic eye. Mean RNFL thickness was not significantly different between eyes in either group. In strabismic amblyopia, mean MT and FV were 5% lower in the sound eye than in the amblyopic eye (MT, 267 microm vs 253 microm, p = 0.005; FV, 2.57 mm(3) vs 2.43 mm(3), p = 0.001). In anisometropic amblyopia, there was no significant difference between eyes in either MT or FV. CONCLUSIONS In patients with strabismic amblyopia, the MT and FV were slightly but significantly lower in the sound eye than in the amblyopic eye. The clinical importance of this difference is not known. No such difference was observed in patients with anisometropic amblyopia.

PHOTODYNAMIC THERAPY FOR VASOPROLIFERATIVE RETINAL TUMORS

Purpose: To report our experience with photodynamic therapy (PDT) with verteporfin for patients with vasoproliferative retinal tumors (VPRTs). Methods: Three patients with VPRTs who presented with macular exudative changes were treated with one session of PDT with 6 mg/m2 body surface area of verteporfin and a light dose of 100 J/cm2 at 689 nm delivered in 166 seconds. Biomicroscopy, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; visual acuity was measured using Early Treatment Diabetic Retinopathy Study criteria. Results: At the 1-year follow-up, all tumors responded with a reduction in size (mean height: pretreatment, 2.96 mm; posttreatment, 1.32 mm), and optical coherence tomography showed complete resolution of macular exudates. For all patients, fluorescein angiography evidenced reduction of leakage from the lesion, and indocyanine green angiography verified nonperfusion of the vascular channels. An improvement in visual acuity (average, 4.7 Early Treatment Diabetic Retinopathy Study letters) was observed. No retreatment was needed. Conclusion: PDT may represent an effective and safe modality of treatment for VPRTs because of its selectivity. Our study supports the application of a light dose of 100 J/cm2, although further studies with larger numbers of cases and longer follow-ups are required.

Photodynamic Therapy with Verteporfin for Symptomatic Circumscribed Choroidal Hemangioma: Five-Year Outcomes

OBJECTIVE To evaluate the long-term efficacy of verteporfin photodynamic therapy (PDT) as the primary treatment for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN Prospective consecutive, 2-centered, noncomparative, interventional case series. PARTICIPANTS Twenty-five subjects with symptomatic CCH. All patients had recent onset of visual symptoms and evidence of exudative macular changes on fluorescein angiography (FA) and optical coherence tomography (OCT). METHODS Verteporfin 6 mg/m(2) body surface area was administered intravenously over a 10-minute interval. Five minutes after infusion, a 689 nm laser was applied with a light dose of 50 J/cm(2) for the first 3 patients and a light dose of 100 J/cm(2) for all the other patients. Retreatments were performed in case of persistent exudation found on OCT. Evaluation of best-corrected visual acuity (BCVA) using Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria, FA, indocyanine green angiography (ICGA), OCT, and ultrasound were performed before PDT and on follow-up examinations. All patients were followed for at least 5 years. MAIN OUTCOME MEASURES Primary outcome measures were changes in BCVA and foveal center thickness (FCT) between baseline and month 60. Secondary measures were tumor thickness decrease, absence of leakage on FA, and adverse events. RESULTS Twenty-two patients received 1 PDT session at 100 J/cm(2), and no recurrences were detected. Three eyes, treated with 50 J/cm(2), received a second PDT session at 100 J/cm(2) 1 month after the first session. After a follow-up of 60 months, BCVA improved an average of 18.5 ETDRS letters (P<0.001); BCVA improved by > or =2 lines in 19 eyes (76%). The FCT decreased from a mean of 386.20 microm to 179.2 microm, and OCT showed the complete resolution of macular exudation in all cases. All tumors responded with a reduction in size. No treatment-related adverse events or complications were identified. CONCLUSIONS The 5-year results of PDT in treating symptomatic CCH support treatment with a light dose of 100 J/cm(2) after slow intravenous infusion of verteporfin to stabilize or improve visual acuity and resolution of macular exudation.