Measurement of Intraocular Pressure with Radiowave Telemetry: Update

1. Measurement of Intraocular Pressure with Radiowave Telemetry: Update Amit Todani, Irmgard Behlau, Mark A. Fava, Fabiano Cade, Miguel Lopez, Samir Melki, Claes Dohlman Massachusetts Eye and Ear Infirmary Harvard Medical School Boston, USA Authors have no financial interest.

2. Background and Significance Tonometers cannot accurately measure the IOP in the presence of a keratoprosthesis (KPro) or artificial cornea.1 Keratoprostheses result in a high corneal rigidity such that they cannot be reliably indented with existing tonometers.1 • About 2/3 of patients with the Boston KPro (Figure) have pre-existing glaucoma.2,3 In addition, significant percentage of these patients develop glaucoma post-surgery.2,3 • Therefore, a reliable IOP sensor that can overcome these limitations has long been desired by KPro surgeons. • Such a device should also prove extremely useful for glaucoma research for continuous measurement of IOP. • We tested a radiowave intraocular telemetry device in vivo in rabbit eyes for long-term biocompatibility and function.

3. Materials and Methods: RIT System ASIC The radiowave intraocular transducer (RIT) is manufactured by Mesotec GmbH, Hannover, Germany (now known as Implandata). The RIT system is comprised of two components: Micro-coil antenna • IMPLANTABLE TRANSPONDER UNIT: • Composed of single application specific integrated • circuit (ASIC) and gold micro-coil antenna. • - Powered by the reader unit placed in proximity • No battery required • Designed for implantation in the human eye • 11 mm diameter x 0.9 mm thickness; 0.1 gram READER: - Powers the sensor - Displays the IOP reading - Placed within 5 cm of the sensor

4. Memory module for device tracking Radiofrequency front end for telemetry On-chip data processing unit 7 5 6 4 3 1 2 Analog-to-digital converter 8 sensor membranes for drift compensation Temperature-sensor 8 sensor membranes for accuracy Materials and Methods: Transponder The RIT transponder is integrated on a single complementary metal oxide semiconductor (CMOS) chip using modern micromachining techniques. It is a fully digital ultra-miniature system that combines pressure-sensor, temperature-sensor, identification encoder, analog-to-digital converter and telemetry into a single application-specific integrated circuit (ASIC) as shown below. The ASIC is bonded to a circular micro-coil antenna made of gold, and hermetically encapsulated in silicone to ensure long-term biocompatibility.

5. Materials and Methods: Transponder The IOP is measured by an array of capacitive pressure sensors as shown in the schematic diagram below. These sensors consist of two parallel plates: a thin flexible membrane which is indented by the IOP and a thicker rigid base. The capacitance between 2 parallel plates is given by the equation C=A/d, where ‘C’ refers to the capacitance, ‘’ refers to the dielectric constant of the medium between the plates, ‘A’ the area of the plates, and ‘d’ refers to the distance between the plates.4 The membrane, being deflected by the IOP changes the distance between itself and the fixed plate, resulting in a capacitance change, the magnitude of which determines the registered IOP.

6. Materials and Methods: Surgical Techniques The transducers (n=6) were sterilized with ethylene oxide. They were implanted either through a corneal autograft (n=2) or through a large limbal incision (n=4) and placed either in the sulcus (n=5) or suspended into the vitreous cavity (n=1) after removing the crystalline lens. As a control for the effects of surgery, in one rabbit (SHAM), the crystalline lens was removed but no implant was placed. The surgical wound was closed with interrupted 10-0 nylon sutures, which were removed after 2 weeks. Post-operatively, daily topical antibiotics (Polytrim) and steroid (Prednisolone acetate 1%) were administered for 6 months. Daily observations and weekly full clinical examinations were performed. The readings obtained by the transducer-readers were compared with those obtained by Tonopen and pneumotonometer.

7. Results: Clinical Observations The transducers were well tolerated, with minimal transient post- operative intraocular inflammation in the early post-operative period that was similar in both the experimental and SHAM groups at comparable time-points. Surgical Sham Rabbit Eye Transducer Rabbit Eye

8. Results: IOP Readings Comparative IOP measurements were obtained under sedation using both the RIT and a Tonopen. The readings obtained by the RIT demonstrated less variability on repeat measurements and had a smaller standard deviation compared to Tonopen. Representative IOP measurements in two rabbits are depicted below.

9. Results: IOP Readings Further comparative IOP measurements were obtained under sedation using RIT, Tonopen, and pneumotonometer. Representative IOP measurements at different timepoints in one rabbit are depicted below. Note: Immediately post-operatively, the readings obtained by the RIT differed from the pneumotonometer and tonopen. This may be due to the RIT being calibrated to operate at the normal intraocular temperature, which was not the case immediately post-operatively. At later time-points, correlation improved.

10. Conclusions • The transducer shows good biocompatibility in vivo (> 12 months in rabbit eyes at present). These rabbits have been off all antibiotics and steroids for > 6 months without adverse effects. • The transducer readings are reproducible and comparable with tonometer and pneumotonometer readings. However, there appears to be some drift in a subset of rabbits. The etiology of transducer drift is being explored. Acknowledgements: Stefan Meyer and Max Ostermeier (Implandata GmbH, Hannover, Germany)

11. Bibliography 1. Khan BF, Harissi-Dagher M, Khan DM, Dohlman CH. Advances in keratoprosthesis: Enhancing retention and prevention of infection and inflammation. Int. Ophthlamol. Clin. 2007;47:61-71. 2. Khan BF, Harissi-Dagher M, Pavan-Langston D, Aquavella JV, Dohlman CH. The Boston keratoprosthesis in herpetic keratitis. Arch Ophthalmology. 2007;125:745-49. 3. Chew HF, Ayres BD, Hammersmith KM, et al. Boston keratoprosthesis outcomes and complications. Cornea 2009;28:989-96. 4. Kakaday T, Hewitt AW, Voelcker NH, Li JS, Craig JE. Advances in telemetric continuous intraocular pressure assessment. Br J Ophthalmol. 2009;93:992-6.