CLÍNICA DE OJOS MALDONADO BAS

1. Arturo Maldonado-Junyent, MD Arturo Maldonado-Bas, MD, PhD CLÍNICA DE OJOS MALDONADO BAS Financial disclosure The Microdevice medical research is sponsored by Artom S.A. CORDOBA - ARGENTINA

2. Microdevice for Treatment of Refractory Glaucoma INTRASCLERAL MICROIMPLANTPATENT Nº 030101897

3. Introduction A new microdevice is introduced for the treatment of refractory glaucoma. Concepts that gave rise to its development are explained as well as its action mechanism and the surgical procedure for its implantation. The results achieved are analyzed. Material and Methods Pre-clinical phase: Examinations were performed in vitro and in vivo to determine the tissue tolerance of the device. 1. Testing in Vitro: a). Agar overlay test. b). Inhibition of cell growth. 2. Testing in vivo: intraperitoneal implantation of the device in rabbits.

4. Clinical phase: Between May 2004 and April 2009, in a multicenter study carried out in Argentina, Peru, Mexico, Venezuela and Brasil, 144 eyes with refractory glaucoma were operated with the study procedure and the study device was implanted. 31.56% of the cases were neovascular glaucomas. Intraocular pressure (IOP) less than or equal to 21 mmHg with or without additional medication was considered as successful. No antimetabolites were used routinely in this series. Features of the device: It consists of two assembled parts: (Figs. 1 and 2) 1. A rectangular body of elasthane™ 5x5mm in diameter perforated at each corner to attach it to the sclera. 2. A silicone tube portion, 10 mm long, 0.4 mm in outer diameter and 0.18 mm in its inner diameter Fig.1: Front view of the device. Fig 2: Side view of the device.

5. Surgical Technique: 1. Dissection of the fornix-based conjunctival flap. 2. Dissection 60% of the thickness of the scleral flap, not less than 6 x 6 mm in diameter (Fig.3). 3. Paracentesis under the scleral flap using a V-Lance knife, and injection of viscoelastic substance. (Fig. 4) 4. Placement of the device, inserting the tubular portion into the anterior chamber through the paracentesis performed in point 3. (Fig. 5. 6) 5. Suturing of the device to the scleral bed with prolene 10/0 or 9/0 (Fig. 7). 6. Repositioning and suturing of the scleral flap with nylon 9/0, covering the device (Fig. 8). 7. Suturing of the conjunctival flap with separate stitches of silk 8/0. Fig 3: Dissection of the scleral flap. Fig 4: Paracentesis using a V-lance. Fig 5: Presentation of the device. Fig. 6: Placement of the device. Fig. 7: Suturing device to the sclera. Fig. 8: Closure of scleral flap.

6. Results: Pre-clinical phase: 1. Testing in Vitro: a). Agar overlay test: The device was placed in an agar plate covered with a monolayer of Vero and NHC cells (human conjunctiva cell line) treated with a vital dye. No loss of staining was observed in cells with the diffusion of soluble toxic substances from the device or from cell lysis after 24 hours of incubation. In conclusion: the material was not toxic to the cell lines studied. b). Inhibition of cell growth: This test is useful to evaluate the presence of extractable cytotoxic substances, in which case it decreases the radius of growth of mammalian Vero and NHC cells. The device was placed in the cell culture medium and after 72 hours was compared with a control cell culture. In conclusion:the material showed no signs of extractable toxicity compared with the group of cells studied. 2. Testing in vivo: The device was implanted in the peritoneum of three rabbits that were sacrificed at thirty days and the sample was processed for anatomic pathology, which reported: partial encapsulation of the material by a very thin fibrous layer, in which very few fibroblasts were identified and very little lymphoplasmacytic infiltrate. In conclusion:no toxicity was observed and virtually no inflammatory response against the material.

7. Clinical phase: The average presurgical IOP was 41.06 mmHg, SD ± 11.53 mmHg with a range between 16 and 70 mmHg. The average IOP at 547 days was 13.45 mmHg, SD ± 3.94 with a range between 8 and 26 mmHg. The average of the latest IOP of each patient was 17.54 with SD ± 9.24 mmHg with a range between 0 and 55 mmHg. Average follow-up was 919 days SD ± 299.71 with a range between 214 and 1793 days. Average success was 73% (105 eyes) of which 57.15% (60 eyes) were regulated with additional medication and 42.85% (45 eyes) without medication. The failure rate was 27% (39 eyes),10 of which (25.7%) were extrusion and the other 29 (74.3%) were due to lack of control of IOP. The average difference between the presurgical and postsurgical IOP was 23.42 mmHg.

8. Complications: For its small size and its location, in no case was any alteration found in eye movement. Early postoperative (at 24 hours): Hypothalamia: resolved without complications, in some cases with medical treatment and in others with intracameral injection of viscoelastic substance. Hyphema: This complication was due to the high percentage of neovascular glaucomas included in this series. In all cases it resolved spontaneously without complications. Choroidal detachment: resolved without further problems with medical treatment. Late postoperative (after 90 days): Subconjunctival tenon’s fibrosis on the scleral flap: This complication was resolved in some of the cases (the others were placed in the group of failures) with surgical resection of fibrotic tenon’s tissue and injecting subconjunctival 5-fluorouracil or with mitomycin C as the attending surgeon preferred. Extrusion of the implant: ten cases of extrusion (25.7%) of failures were reported in this series. The videos of the surgeries were reviewed and failure of surgical technique was found in eight cases (making a thin scleral flap, less than 6x6 mm, so that the tissues were sutured with tension). We believe that it is very important for the scleral flap to be thick, 6x6 mm, and if there is any possibility that the device might remain under tension, a scleral pocket can be made. Fig 9. Fig 9: scleral pocket

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