Alex Malandrini

An In Vivo Confocal Microscopy Analysis of Effects of Topical Antiglaucoma Therapy With Preservative on Corneal Innervation and Morphology

PURPOSE To evaluate the long-term effects of preservative-free and preservative-containing antiglaucoma eye drops on the tear secretion and ocular surface. DESIGN Comparative retrospective study. METHODS A total of 84 patients with bilateral primary open-angle glaucoma or ocular hypertension divided into 5 groups according to type of topical hypotensive therapy and 20 healthy age-matched volunteers were studied. Clinical tests (corneal sensitivity, Schirmer I test, and lachrymal film break-up time), and in vivo confocal microscopy were performed in all patients. RESULTS A significant reduction of the scores was found between groups on topical hypotensive therapy and the control group in all clinical parameters studied (P < .05). In particular, the clinical scores were significantly lower in the preservative medication groups than in the preservative-free group (P < .05). The density of superficial epithelial cells was reduced in all glaucomatous patients, except for the preservative-free group (P > .05), with respect to control subjects (P < .001). On the contrary, the density of basal epithelial cells of glaucomatous preservative therapy groups was higher than control and preservative-free groups (P < .05). Stromal keratocyte activation and the number of beads were higher in all glaucoma preservative groups (P < .05). The number of sub-basal nerves was lower in all glaucoma groups than in the control group (P < .05) and tortuosity was significantly higher in glaucoma than control groups (P < .05). Reflectivity of fibers did not show any significant difference between the 6 groups (P < .05). CONCLUSIONS Glaucomatous patients with chronic treatment show ocular surface alterations. The development of nontoxic antiglaucoma treatment may reduce damage to the ocular surface and improve the compliance and the adherence in the medical therapy.

Diagnosis and management of traumatic cyclodialysis cleft

A 48-year-old man presented with hyphema, iridocyclitis, iridophacodonesis, and maculopathy after a contusive trauma. Ultrasound biomicroscopy identified a 90-degree cyclodialysis cleft with severe damage of the zonular fibers. Echographic B-scan examination revealed intravitreal hemorrhage and a 360-degree choroidal detachment. One month later, phacoemulsification was performed and a single-piece poly(methyl methacrylate) intraocular lens was inserted into the ciliary sulcus, with the haptic rotated toward the cyclodialysis cleft area. Postoperatively, the visual acuity improved and the intraocular pressure returned to normal. Ultrasound biomicroscopy showed closure of the cleft by reattachment of the ciliary body to the scleral spur. Optical coherence tomography revealed complete resolution of the macular and choroidal folds. Ultrasound biomicroscopy is a useful method for appropriate management of traumatic cyclodialysis cleft. In cases of small cyclodialysis clefts, with the surgical method we describe, the lens haptics apply directional force toward the sclera, fostering adherence of the ciliary body fibers.

Phacoemulsification without intraocular lens implantation in patients with high myopia: Long-term results

Purpose: To estimate the cumulative incidence of postoperative retinal detachment (RD), rhegmatogenous retinal lesions requiring argon laser treatments, anterior (ACO) and posterior (PCO) capsule opacification, and neodymium:YAG (Nd:YAG) laser capsulotomy in patients with high myopia who had phacoemulsification without intraocular lens (IOL) implantation. Setting: Department of Ophthalmology and Neurosurgery, University of Siena, Siena, Italy. Methods: Seventy‐three eyes of 57 patients with high myopia who had phacoemulsification without IOL implantation from 1993 to 1996 were retrospectively reviewed. The mean postoperative follow‐up was 62.3 months and the mean axial length, 30.22 mm (range 29.10 to 33.70 mm). The incidence of RD and preoperative and postoperative prophylactic argon laser photocoagulation for rhegmatogenous retinal lesions were assessed. Between 1997 and 2000, ACO was evaluated subjectively and PCO was evaluated using the EPCO photographic image‐analysis system. The incidence of Nd:YAG laser capsulotomy was noted. Results: Argon laser photocoagulation was performed in 8 eyes (10.9%) preoperatively and 3 eyes (4.1%) postoperatively. One RD (1.3%) was observed 26 months after surgery; no preoperative or postoperative prophylactic argon laser photocoagulation or Nd:YAG laser capsulotomy was performed in this eye. At 1 year, 49 eyes (67.1%) had mild ACO and 24 (32.8%) had anterior capsule fibrosis. The data did not change during subsequent follow‐up visits. At 6 years, the mean PCO grade was 1.109 (range 0.972 to 2.931); an Nd:YAG laser capsulotomy was performed in 12 eyes (16.4%). Conclusions: Compared with other studies that evaluated the outcomes of highly myopic patients who had cataract surgery with posterior chamber IOL implantation, our patients, who did not have IOL implantation, had a lower incidence of postoperative rhegmatogenous retinal lesions requiring argon laser treatments and a similar incidence of postoperative RD and visually significant PCO.

In vivo confocal microscopy in a patient with recurrent conjunctival intraepithelial neoplasia

and redness in the right eye (RE) was referred for a clinical evaluation. A 2-year history of corneal ulcer in the RE was elicited. The subject had also undergone pterygium surgery in the same eye at another ophthalmology centre 11 years previously. His left eye (LE) was amblyopic. Best corrected visual acuity (BCVA) was 20 ⁄ 100 LE and 20 ⁄ 200 RE. Slit-lamp examination revealed an area of epithelial defect with a minimally elevated and vascularized patch of leucoplakia that was located inferonasally in the cornea of the RE. The lesion extended to the central portion of the cornea. Lesion borders were indistinct. Bulbar conjunctiva was diffusely congested (Fig. 1A). Corneal scrapings from the ulcer were negative for micro-organisms. No abnormality was present in the LE. Examination by corneal confocal microscopy (CM) was carried out using the HRT II Rostock cornea module (Heidelberg Engineering GmbH, Heidelberg, Germany), in which the x and y positions and section depth are controlled manually. Prior to examination, 0.4% oxibuprocaine chlorhydrate (Novesina ; Novartis Farma, Varese, Italy) and a gel tear substitute (Genteal gel ; Novartis Farma, Varese, Italy) were applied into the inferior conjunctival fornix. Confocal microscopy showed irregular hyperreflective areas with numerous bright elements at the level of the superficial cell layer of the corneal epithelium in the RE. The epithelial cells near the lesion were significantly larger in size and had more irregularities in shape and borders. Furthermore, the nuclei were particularly bright. The distinction between healthy and pathological epithelium appeared very clear (Fig. 1C, D). Eight months later, an excisional biopsy with cryotherapy to the bare sclera was performed. The histo-pathological examination revealed diffuse epithelial atypia, consistent with corneal and conjunctival intraepithelial neoplasia (CIN). After surgery, complete resolution of the limbal and corneal lesions with mild paracentral corneal scarring was noted (Fig. 1B). Best corrected VA was 20 ⁄ 60 in the RE. Six months later, the patient underwent a penetrating keratoplasty (PK) in the RE. Pathological examination of the corneal button revealed normal corneal epithelium and an intact basement membrane. The patient was observed for 9 months after PK without recurrence (Fig. 2A). Nine months later, when the patient returned for a longterm follow-up visit, slit-lamp examination of the RE showed corneal recurrence of CIN as multiple, faintly demarcated, small islands of peripheral corneal epithelial opacities and persistent epitheliopathy on the nasal and inferior graft (Fig. 2B, C). Confocal microscopy confirmed lesions characteristic of CIN, with larger, irregular, bright cells with hyperreflective larger nuclei in the superficial epithelium. Some cells presented two bright intracellular bodies. In this case, the distinction between abnormal and normal epithelial cells was not very clear (Fig. 2D–F). Confocal microscopy is an imaging method that allows real-time, noninvasive optical microscopic sectioning of the ocular surface (Chiou et al. 2006). Duchateau et al. (2005) explored CIN using CM for the first time. The main pathological lesions detected by histopathology were confirmed by CM. Although CIN is a slowly progressive condition with a small risk of malignant potential, recurrence rates are high if traditional therapies are used (Basti & Macsai 2003). Because of the subsequent risk of recurrence with standard treatments, and because repeated surgery can cause Diagnosis ⁄Therapy in Ophthalmology

In vivo confocal microscopy in recurrent granular dystrophy in corneal graft after penetrating keratoplasty

Two case reports of recurrent granular dystrophy in corneal grafts after penetrating keratoplasty are presented. Slit‐lamp examination and confocal microscopy (HRT II) were performed in two patients with recurrent granular dystrophy. All confocal microscopic findings of granular dystrophy were evaluated in the graft. Dystrophic lesions of the donor cornea presented the same confocal microscopic aspects in both eyes, and were similar to granular dystrophy lesions. Confocal microscopy is an imaging method that may provide new information on corneal microanatomy in dystrophies. It may be particularly useful in improving the early diagnosis of dystrophic lesions in corneal grafts.

Air-guided manual deep anterior lamellar keratoplasty: long-term results and confocal microscopic findings

Purpose To evaluate the long-term results of air-guided manual deep anterior lamellar keratoplasty (DALK) and to perform confocal microscopy on postoperative DALK corneas. Methods Seven postoperative consecutive DALK corneas were evaluated 1 year after suture removal. All patients underwent a complete ophthalmologic examination evaluating visual acuity, astigmatism, corneal thickness, and endothelial cell count. Confocal microscopy was performed to examine the corneas of the seven eyes and to obtain the measured interface depth. Results Eighteen months after surgery, the mean postoperative uncorrected visual acuity was 20/38 and the mean best-corrected visual acuity was 20/23. Postoperative mean value of residual recipient stroma thickness was 65.57 μm ± 28.74. Conclusions Maximum depth DALK can lead to significant advantages for quality of vision when compared to other types of anterior lamellar keratoplasty. Still, it remains a challenging procedure. These results show that a deep dissection without baring Descemet membrane makes good visual results possible, preventing corneal perforation and conversion to penetrating graft.

Morphologic study of the cornea by in vivo confocal microscopy and optical coherence tomography after bifocal refractive corneal inlay implantation

Purpose To evaluate the biocompatibility of the Flexivue Microlens intracorneal inlay based on healing of corneal wounds and analysis of corneal structural features using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS‐OCT). Setting Ophthalmology Department, Misericordia e Dolce Hospital, Prato, Italy. Design Case series. Methods The intracorneal inlay was inserted in a stromal pocket created in the nondominant eye of emmetropic presbyopic patients using a femtosecond laser. In vivo confocal microscopy and AS‐OCT examinations were performed preoperatively and 1, 6, and 12 months postoperatively. Results The mean follow‐up was 7.6 months. In the early postoperative period, IVCM showed intense cellular activity in the stroma around the inlay, edema, inflammation, and degenerative material deposition but normal regularity after 12 months. Anterior segment OCT showed a regular planar shape of the corneal pocket in all eyes. The mean of the side‐cut angles was 30.7 degrees. The mean difference between the measured and planned pocket depth was 9.77 &mgr;m. At 1 month, hyperreflective areas beneath the inlay and microfolds were observed in 21 of the 52 eyes. After 12 months, the anterior segment profile was regular and interface pocket reflectivity decreased over time. Six patients had inlay removal postoperatively (3 before 6 months; 3 before 12 months); after removal, IVCM and AS‐OCT showed clear corneas without signs of irregularity. Conclusion In vivo confocal microscopy and AS‐OCT analysis showed that the inlay elicited a low‐level wound‐healing response in its immediate vicinity with no alteration in the corneal structures. Financial Disclosure Dr. M. Fantozzi is a member of the Presbia medical advisory board. No other author has a financial or proprietary interest in any material or method mentioned.

Laser-Assisted Penetrating Keratoplasty: 1-Year Results in Patients Using a Laser-Welded Anvil-Profiled Graft

PURPOSE To describe a new laser-assisted penetrating keratoplasty technique combining a femtosecond anvil-like trephination pattern with the laser welding procedure. DESIGN Cohort prospective study with 1 year of follow-up (June 2011 through January 2013). METHODS This study was performed at Misericordia e Dolce Public Hospital, Prato, Italy. Twenty-four eyes of 22 patients underwent penetrating keratoplasty: 4 had granular dystrophy, 12 had keratoconus in its final stages, 3 had post-herpetic leukoma, and 5 had corneal scars. A femtosecond laser was used to create anvil-profiled cuts in donor and recipient corneas. Diode laser welding was performed, supporting standard suturing. All patients were evaluated for corrected distance visual acuity, pachymetry, manifest astigmatism, and endothelial cell density after 1, 3, 6, and 12 months. RESULTS Mean ± standard deviation postoperative corrected visual acuity was 0.48 ± 0.23 logarithm of the minimal angle of resolution (logMAR), 0.30 ± 0.18 logMAR, 0.18 ± 0.13 logMAR, and 0.13 ± 0.16 logMAR at 1, 3, 6, and 12 months, respectively. At the same follow-up times, mean pachymetry was 537 ± 57 μm, 533 ± 74 μm, 528 ± 72 μm, and 529 ± 58 μm, respectively; and mean endothelial cell density was 1945 ± 371 cells/mm(2), 1881 ± 410 cells/mm(2), 1781 ± 401 cells/mm(2), and 1730 ± 376 cells/mm(2), respectively. Mean manifest and topographic postoperative astigmatism were: 3.6 ± 2.5 diopters (D) and 4.65 ± 2.57 D at 1 month, 2.93 ± 2.34 D and 4.79 ± 2.85 D at 3 months, 2.82 ± 1.75 D and 3.44 ± 2.28 D at 6 months, and 2.08 ± 1.25 D and 2.73 ± 2.01 D at 12 months, respectively. All surgical operations were successful and without intraoperative complications. CONCLUSIONS The use of the anvil trephination profile was effective for performing laser-assisted penetrating keratoplasty. The large donor-recipient interface enables the laser welding procedure and good preservation of the recipients endothelial cell pool.

Bifocal refractive corneal inlay implantation to improve near vision in emmetropic presbyopic patients.

Purpose To evaluate the safety and effectiveness of the Flexivue Microlens corneal inlay for the improvement of near vision in emmetropic presbyopic patients. Setting Ophthalmology Department, Misericordia e Dolce Hospital, Prato, Italy. Design Prospective interventional case series. Methods Corneal inlay implantation was performed in nondominant eyes using a 150 kHz femtosecond laser (iFS). Refraction, uncorrected (UNVA) and corrected (CNVA) near visual acuities, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, slitlamp evaluation, wavefront aberrometry, photopic and mesopic contrast sensitivity, anterior segment optical coherence tomography, endothelial cell density, and central corneal thickness measurements were assessed preoperatively and at each postoperative visit. Results The study evaluated 81 eyes. In 26 eyes, the mean preoperative UNVA and UDVA were 0.76 logMAR and 0.00 logMAR, respectively, compared with 0.10 logMAR and 0.15 logMAR, respectively, 36 months postoperatively. Sixteen (62%) of 26 treated eyes lost more than 1 line of UDVA, and 5 (19%) lost more than 2 lines of UDVA. Two eyes (8%) lost more than 1 line of CDVA at 36 months. The mean binocular UDVA was 0.00 logMAR preoperatively and 0.02 logMAR at 36 months. The mean spherical aberration increased after surgery. Statistically significant differences in the mean mesopic and photopic contrast sensitivities at higher spatial frequencies were found between treated eyes and nontreated eyes. Explantation was performed in 6 treated eyes because of halos, glare, and a reduced UDVA. Conclusion The corneal inlay might be a safe and effective method of improving UNVA in emmetropic presbyopic patients. Financial Disclosure Dr. Fantozzi is a member of the Presbia medical advisory board. No other author has a financial or proprietary interest in any material or method mentioned.

Growth of congenital malignant teratoid medulloepithelioma of the ciliary body: a case study

The purpose of this study was to describe the growth pattern of congenital malignant teratoid medulloepithelioma of the ciliary body by reporting clinical and imaging findings with pathological correlation. An 11-month-old little girl presented with a whitish-pink iris mass in the right eye resulting from a small ciliary body mass consistent with medulloepithelioma at both clinical and computed tomography (CT) findings. At CT, the lesion showed heterogeneous attenuation, without intraocular calcifications. Eleven months later, clinical and ultrabiomicroscopy showed a clear enlargement of the mass, which invaded the pupil. At magnetic resonance imaging (MRI), the lesion showed T1-weighted hyperintensity and T2-weighted slight hypointensity when compared to the vitreous and a notch in the anterolateral aspect of the ipsilateral lens. After intravenous gadolinium administration, the lesion showed intense homogeneous enhancement, and there was leakage of gadolinium in the anterior chamber, resulting from impairment of blood-aqueous barrier. Biopsy revealed a malignant teratoid medulloepithelioma. The eye was then enucleated, and histology confirmed the diagnosis. Systemic chemotherapy and radiotherapy were not performed, since there was no extraocular extension. The 57-month clinical and MRI follow-up did not show disease relapse. This uncommon case displays the natural history of congenital malignant teratoid medulloepithelioma of the ciliary body. While the tumour might have been successfully treated by local excision at diagnosis, the delay in surgical treatment led to tumour overgrowth with consequent need for enucleation. The most important prognostic feature is extraocular extension, which carries a risk of local recurrence, eventually resulting in intracranial extension and/or lymphatic spread.