Marco Coassin

An In Vitro Intact Globe Expansion Method for Evaluation of Cross-linking Treatments

PURPOSE To measure the tissue mechanical response to elevated intraocular pressure (IOP) using intact globe expansion of rabbit eyes. This method examined rabbit kit (2-3 weeks old) eyes as a model for weakened tissue and evaluated riboflavin/UVA and glyceraldehyde cross-linking treatments. METHODS The ocular shape of enucleated eyes was photographed during a 24-hour period while a controlled IOP was imposed (either low IOP = 22 mm Hg or high IOP = 85 mm Hg). Untreated controls consisted of kit eyes tested at both low- and high IOP and adult eyes tested at high IOP. Treated kit eyes (dextran controls, riboflavin/UVA treatment of the cornea, and glyceraldehyde treatment of the entire globe) were tested at high IOP. RESULTS Low IOP elicited negligible creep of the sclera and very gradual creep of the cornea. In contrast, high IOP induced up to an 8% strain in the sclera and a 15% strain in the cornea of rabbit kit eyes. The expansion of adult eyes was less than one third that of kit eyes at the same, high IOP. Riboflavin/UVA treatment of corneas reduced expansion compared with that in both dextran-treated and untreated control corneas. Glyceraldehyde treatment prevented expansion of the cornea and sclera. CONCLUSIONS The intact globe expansion method (GEM) imposes a loading geometry comparable to in vivo conditions and can quantify changes in mechanical stability as a function of testing conditions (e.g., IOP, tissue maturation, and therapeutic cross-linking) with small sample sizes and small variability. Rabbit kit eyes provide a model of weak tissue suitable for screening treatments that strengthen the cornea and sclera.

Hypothermia reduces secretion of vascular endothelial growth factor by cultured retinal pigment epithelial cells.

Aim Visual loss in age-related macular degeneration usually develops secondary to choroidal neovascularisation. Vascular endothelial growth factor (VEGF) is a critical regulator of retinal angiogenesis and vascular permeability, especially in hypoxic conditions. We hypothesise that hypothermia may reduce the retinal pigment epithelium (RPE) metabolism and, consequently, the levels of VEGF secretion by cultured RPE cells under hypoxic conditions. The effects of hypothermia were compared with the metabolic inhibiting effects of thiopental and nicotinamide. Methods ARPE-19 cells were grown in culture for up to 5 days under normoxic (20% O2) and hypoxic (1% O2) conditions at temperatures ranging from 27°C to 40°C. For experiments with pharmacological agents, thiopental and nicotinamide were added to the media. VEGF levels in the media were measured by ELISA and cell metabolic activity was measured by a fluorescent cell metabolic assay. Results We found that hypothermia reduced ARPE-19 cell metabolism in a temperature-dependent fashion. Hypothermia also reduced ARPE-19 cell VEGF secretion in a temperature-dependent fashion. ARPE-19 cell VEGF secretion was reduced by 38% at 34°C compared with cells grown at 37°C. Conversely, ARPE-19 cell VEGF secretion was increased by 32% at 40°C compared with cells grown at 37°C. Hypoxia increased ARPE-19 cell VEGF secretion by 84% at 37°C. However, hypothermia decreased the hypoxia-induced increase of ARPE-19 cell VEGF secretion by 30%. The effect of hypothermia on ARPE-19 cell VEGF secretion was reversible after 4 days. In contrast to hypothermia, thiopental and nicotinamide were able to reduce RPE cell metabolism but not VEGF secretion. Conclusion Hypothermia decreases both VEGF secretion and cellular metabolism in ARPE-19 cells. Hypothermia also mitigates the hypoxia-induced increase in ARPE-19 cell VEGF secretion. These effects of hypothermia are potentially unique and cannot be obtained by other pharmacological agents that slow cellular metabolism.

Bromfenac ophthalmic solution 0.09% as an adjunctive therapy to topical steroids after cataract surgery in pseudoexfoliation syndrome.

Purpose To study with laser flare photometry the antiinflammatory effect of bromfenac added to a topical steroid versus a topical steroid alone in patients with pseudoexfoliation (PXF) syndrome after cataract surgery. Setting Ophthalmology Unit, Santa Maria Nuova Hospital, Reggio Emilia, Italy. Design Randomized clinical trial. Methods Patients with cataract and clinical signs of PXF were randomized to dexamethasone 0.1% and tobramycin 0.3% ophthalmic solution (Group 1) or with the adjunct of bromfenac ophthalmic solution 0.09% (Group 2). All patients were examined on the day of surgery (baseline) and postoperatively at 1, 3, 7, and 30 days. Laser flare photometry was used to quantify anterior chamber inflammation and optical coherence tomography to measure macular thickness. Results Sixty‐two patients were included. Postoperatively, the mean flare was 31% lower in Group 2 than in Group 1 at 3 days (11.92 ph/msec ± 8.14 [SD] versus 17.13 ± 9.03 ph/msec; P = .025) and 43% lower at 7 days (10.77 ± 6.17 ph/msec versus 18.72 ± 12.37 ph/msec; P = .003). There were no significant differences in postoperative visual acuity, symptoms, or ocular pain between groups. The mean macular thickness 1 month after surgery was increased in Group 1 but not Group 2; the difference between groups was significant at 4 weeks (P = .03). The incidence of intraretinal cysts was higher in Group 1 (n = 4) than in Group 2 (n = 0). Conclusion The addition of bromfenac to topical steroids after cataract surgery in eyes with PXF was associated with greater reductions in inflammation than steroids alone. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Fluocinolone Acetonide Implant (Retisert) for Chronic Cystoid Macular Edema in Two Patients with AIDS and a History of Cytomegalovirus Retinitis

Purpose: To report the authors’ experience using fluocinolone acetonide (Retisert) to treat cystoid macular edema (CME) resulting from immune recovery uveitis (IRU) in 2 acquired immunodeficiency syndrome (AIDS) patients with a history of cytomegalovirus (CMV) retinitis. Design: Interventional case series. Methods: Medical records were reviewed of 2 patients who received Retisert implantation in 3 eyes for IRU-associated inflammation and CME. Suppression of CMV disease was achieved with oral medication in one patient and with simultaneous implantation of a ganciclovir implant in the other patient. Results: After Retisert implantation in 3 eyes in AIDS patients on HAART, improvement in CME was seen in 2 eyes. No CMV reactivation was detected during the several-month follow-up period. Conclusions: Retisert may be an effective treatment for CME in AIDS patients with IRU reactivation and a history of CMV retinitis.

Optical coherence tomography for retinal metastasis with unknown primary tumor.

The authors describe the optical coherence tomography (OCT) findings and the therapeutic approach of a patient with metastatic neoplastic disease of the retina. A patient with a history of brain cancer of undetermined origin underwent imaging and surgery to investigate a suspected metastatic retinal lesion of the right eye. Retinal thinning with cordon-like hyperreflective structures was seen on OCT. Neoplastic cells consistent with small cell carcinoma were identified in the vitreous sample. Those cells were thought to be similar to the previous biopsied cerebellar tumor specimen. OCT imaging, along with vitrectomy and retinal biopsy, may be useful in the evaluation of patients with suspected metastatic lesions of the retina.

Cataract surgery in patients with pseudoexfoliation syndrome: current updates

Pseudoexfoliation is a ubiquitous syndrome of multifactorial origin affecting elderly people by increasing the risk of cataract and secondary glaucoma development. Despite modern techniques and technologies for cataract surgery, pseudoexfoliation syndrome represents a challenge for surgeons because of the increased weakness of the zonular apparatus and limited pupil dilation. Due to the inherent difficulties during surgery, the risk of vitreous loss in these patients is several times higher than in cataract patients without pseudoexfoliation. Using currently available surgical devices (ophthalmic viscosurgical device, iris retractors and ring dilators, capsular tension ring, etc.), the risk of intraoperative complications may be much reduced, allowing the surgeon to handle difficult cases with greater confidence and safety. This review analyzes the methodologic approach to the patient with zonular laxity with the aim of providing useful advices to limit the risks of intraoperative and postoperative complications. From the preoperative planning, to the intraoperative management of the small pupil and phacodonesis, and to the postoperative correction of capsule phimosis and intraocular lens dislocation, a step approach to the surgical management of pseudoexfoliation patients is illustrated.

Big bubble DALK after CXL in keratoconic patients

Collagen cross-linking (CXL) is being offered to a growing number of keratoconic patients worldwide for prevention of disease progression, with an overall success rate that exceeds 90% of the treated eyes.1,2 However, some patients do continue to progress after CXL and may need to undergo keratoplasty. Deep anterior lamellar keratoplasty (DALK) has become the preferred technique by an increasing number of surgeons for surgical correction of patients with moderate and severe keratoconus with poor corrected distance visual acuity (CDVA).3 The “Big Bubble” technique for DALK allows cleavage separation between Descemet’s membrane (DM) and posterior stroma by forceful injection of air into the deep stroma.3,4 DALK with baring of DM has been associated with better visual outcomes when compared to DALK by means of deep stromal manual dissection.4,5 Overall success in separating DM from the overlying tissue with this technique has been reported to be approximately 70% to 80% worldwide.4,5 CXL produces a compaction of collagen fibers that is confined to the anterior 250 μm of the corneal stroma, as has been shown on electrophoresis ex vivo and confocal scanning laser microscopy in vivo.6-9 Nonetheless, compaction of the anterior stroma could theoretically hinder formation of the “Big Bubble” cleavage plane in the posterior stroma and therefore concerns have been raised about the possibility of performing a successful “Big Bubble” technique in corneas previously treated with CXL.10 We report a series of patients who had CXL and underwent the “Big Bubble” technique for DALK for keratoconus progression. Data are expressed as mean ± standard deviation. Nine eyes of 9 patients (6 males, 3 females; mean age: 31.3 ± 7.8 years) were included in this series. All patients underwent CXL (6 epitheliumoff, 3 transepithelial). Visual and topographic disease progression was detected in all patients at 3 months after CXL. The mean time between CXL and DALK was 11 ± 7.8 months. CDVA before DALK was 20/50. The corneal thinnest point before DALK measured by anterior segment optical coherence tomography (Visante; Carl Zeiss Meditec, Jena, Germany) was 410 ± 22 μm. Preoperative maximum keratometric value (Eye top; CSO, Florence, Italy) was 56.2 ± 2.5 diopters (D) and average keratometric value was 49.1 ± 1.7 D. Procedures were performed by two surgeons (AC, LF) with the aid of a 27-gauge cannula (Fogla Cannula; Bausch & Lomb/Storz Ophthalmics, Tuttlingen, Germany) for intrastromal air injection. Formation of Big Bubble was successful in 8 of 9 eyes. In one eye, DALK was completed by manual dissection without complications. Of interest, this eye had undergone an epithelium-off CXL procedure. After complete removal of corneal sutures (1 year postoperatively), CDVA was 20/25 and maximum and average keratometric values were 44.3 ± 0.7 and 42.6 ± 0.8 D, respectively. In this small series, the “Big Bubble” technique for DALK after CXL appeared to be at least equally successful compared to the same procedure carried out in corneas without CXL. A history of previous CXL in keratoconic patients should not discourage surgeons from performing this procedure.

Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to Presumed Intraocular Tuberculosis

ABSTRACT Purpose: To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB). Methods: Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months. Results: Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded. Conclusions: IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.

Vitreoretinal lymphomas misdiagnosed as uveitis: Lessons learned from a case series.

Purpose: To present challenging cases of vitreoretinal lymphoma (VRL) that was misdiagnosed as uveitis because of the apparent intraocular inflammation. At the light of the new classification of intraocular lymphomas, we detail the characteristics that masqueraded the tumors and the clinical aspects that guided us to the correct diagnosis. Materials and Methods: We retrospectively reviewed the patients referred to our uveitis service between January 2006 and December 2014. Results: Seven patients referred with a presumptive diagnosis of idiopathic uveitis received a final diagnosis of VRL. The median time between the onset of symptoms and definitive diagnosis was 25 months for these complex cases. The median time from presentation at our clinic to final diagnosis was 1 month. The described clinical features including dense vitreous cells and subretinal infiltrates were characteristic and tend to be present in all these chronically ill patients. Vitreous samples were collected, and all demonstrated the pathognomonic tumor cells, the specific immunoglobulin heavy chain gene rearrangements, and an interleukin (IL)-10 to IL-6 ratio >1. Conclusion: VRLs are severe diseases with a poor prognosis that may be misdiagnosed as idiopathic inflammatory conditions of the eye. Treatment with steroids may occult the tumors and delay the correct diagnosis. Appropriate evaluation may prompt to a timely vitreous sampling and therefore to a faster diagnosis in these peculiar cases where the correct diagnosis was delayed by several months.

Restraining Inflammation in Pseudoexfoliation Syndrome

P atients with pseudoexfoliation syndrome (PEX) experience more intense inflammation after phacoemulsification compared to routine cataracts. The effect of topical nonsteroidal anti-inflammatories (NSAIDs) in eyes with PEX have not been studied to date. Laser flare photometry was used in this study to evaluate subtle amounts of postoperative inflammation. The addition of bromfenac to dexamethasone ophthalmic solution significantly reduced anterior chamber inflammation after cataract surgery in PEX when compared to dexamethasone alone. Postoperative macular thickness at optical coherence tomography (OCT) was also positively affected by the addition of topical bromfenac.