Ophthalmology 2020 Projects

Project Title: A retrospective chart review identifying the risk factors predisposing Retinitis Pigmentosa patients to Cystoid Macular Edema

Faculty Mentor: Jinghua Chen 
Email: jinghuachen@ufl.edu 

Student: Elizabeth Dawson
Email: elizad@ufl.edu 

Research Project Description:

Cystoid macular edema (CME) is a common sequela in patients with Retinitis Pigmentosa (RP), a group of degenerative retinal diseases categorized as rod-cone dystrophies and associated with mutations in roughly 90 genes inherited either autosomal recessive, autosomal dominant, or X-linked (1). RP presents with night blindness and gradual loss of peripheral vision, progressing to loss of central vision and legal blindness in the end stages of the disease. There is no definitive cure for RP, though gene therapies are being developed and are currently used in a subset of patients with biallelic RPE65 mutations (2). CME greatly diminishes central visual function and is estimated to affect almost a third of RP patients (3). It is a sign of ocular disease and found in a variety of conditions including post-surgery, diabetes, hypertensive retinopathy, and vascular occlusion (4). CME pathogenesis is hypothesized to be the extracellular accumulation of fluid in the internal retinal layers surrounding the fovea due to the degradation of the blood-retinal barrier and leakage of the retinal pigment epithelium (5). Another study found that fluid accumulation occurs in the inner nuclear layer of the retina, initiated by a compromised deep capillary plexus (6).

While treatment of underlying RP is currently impractical for most patients, vision decline due to CME is readily treatable. Therapies of CME are aimed at reducing fluid accumulation through the oral or topical carbonic anhydrase inhibitors (CAIs) acetazolamide and dorzolamide, intravitreal corticosteroids, the anti-vascular agent Bevacizumab (anti-VEGF monoclonal antibody) and pars plana vitrectomy (7). Initially, evaluating RP patients for CME was difficult because angiographic evidence of leakage was not always present. Current methods utilize optical coherence tomography (OCT) to monitor and identify CME even before decreases in visual acuity (8). Identifying those who may be at highest risk for developing CME could aid ophthalmologists in maintenance of their patients with RP.

The purpose of this study is to identify risk factors and analyze visual outcomes of cystoid macular edema in retinitis pigmentosa patients. Being able to identify those patients at highest risk of developing CME would allow ophthalmologists to employ therapies before vision is significantly impaired. Due to the large number of patients with RP at the UF Health Eye Center, our goal is to identify risk factors that predispose these patients to developing CME, thus providing more timely care.

In conducting this retrospective chart review, we will investigate the relationship between vision deterioration associated with CME in retinitis pigmentosa (RP) patients and factors such as age and co-morbid disease to better identify the populations of patients at the highest risk for developing CME. Patients identified as high risk can be better monitored with optical coherence tomography (OCT) for signs of macular edema, and treatment with acetazolamide or dorzolamide can be initiated to delay central vision loss. Our aim is to investigate the risk factors of developing CME in RP patients including age, gender, ocular comorbidities, systemic comorbidities, gene mutation, years since diagnosis, analyze different treatment and responses, and study longitudinal vision change and the course of CME with or without treatment.

References:

  1. Diakatou, M., Manes, G., Bocquet, B., Meunier, I., & Kalatzis, V. (2019). Genome editing as a treatment for the most prevalent causative genes of autosomal dominant retinitis pigmentosa. International journal of molecular sciences, 20(10), 2542.Patel, U., Boucher, M., de Léséleuc, L., & Visintini, S. (2018). Voretigene neparvovec: an emerging gene therapy for the treatment of inherited blindness. In CADTH Issues in Emerging Health Technologies. Canadian Agency for Drugs and Technologies in Health.
  2. Hajali, M., & Fishman, G. A. (2009). The prevalence of cystoid macular oedema on optical coherence tomography in retinitis pigmentosa patients without cystic changes on fundus examination. Eye, 23(4), 915-919.
  3. Joussen, A. M., & Wolfensberger, T. J. (2013). Mechanisms of macular edema and therapeutic approaches. Retina, 1, 590-604.
  4. Cunha-Vaz, J., & Travassos, A. (1984). Breakdown of the blood-retinal barriers and cystoid macular edema. Survey of Ophthalmology, 28, 485-492.
  5. Yeo, J. H., Kim, Y. J., & Yoon, Y. H. (2020). OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH RETINITIS PIGMENTOSA-ASSOCIATED CYSTOID MACULAR EDEMA. Retina (Philadelphia, Pa.).
  6. Bakthavatchalam, M., Lai, F. H., Rong, S. S., Ng, D. S., & Brelen, M. E. (2018). Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review. Survey of ophthalmology, 63(3), 329-339.
  7. Strong, S., Liew, G., & Michaelides, M. (2017). Retinitis pigmentosa-associated cystoid macular oedema: pathogenesis and avenues of intervention. British Journal of Ophthalmology, 101(1), 31-37.

Project Title: A longitudinal comparative study on retinitis pigmentosa patients with or without glaucoma and potential effects on optical coherence tomography, visual field examination, and medical intervention

Faculty Mentor: Siva Lyer 
Email: ssr@ufl.edu 

Student: Alex Weaver 
Email: acweave@ufl.edu  

Research Project Description:

Cataract surgery in the United states is noted as one of the most rapidly expanding surgical procedures by number, with an estimated doubling of 24.4 million cases in 2010 to 50 million by 2050 1-2. Under ideal conditions the intraocular lens (IOL) is placed within the capsular support structure following surgical removal of the cataract or otherwise damaged lens. In cases presenting with absent or structurally inadequate capsules, alternative IOL placement techniques including iris fixation, scleral fixation, and anterior chamber placement are implemented. Given the range of options there is still no consensus on which approach produces optimal outcomes with the fewest complications. In response to novel posterior chamber approaches, this paper will limit comparison to a single chamber and will therefore exclude anterior IOL placements3-4. A common risk for these non-ideal IOL placements is the potential for post-operative lens decentration, tilt, or other alterations that may require additional surgery or medical management5-9. A better understanding of which technique provides optimal vision capability with fewer complications could streamline surgical decision making and improve patient safety.

The University of Florida Department of Ophthalmology implements a variety of approaches to the fixation of a posterior chamber IOL. By conducting a retrospective chart review of surgical outcomes and complications, we predict that one of the conducted approaches will show superior improvement in range of outcome measures, primarily best corrected visual acuity, in relation to the other selected approaches. The rationale is built on the existing data of individual level outcome measures but a lack of relative procedural data comparison.

We will present a case series to determine the outcomes of varied posterior chamber IOL fixation techniques, in which we will compare the objective measures of surgically repaired visual function and other quantitative measures of resulting complications and surgical efficiencies.

References:

  1. Cataract Data and Statistics | National Eye Institute. Published July 17, 2019. Accessed April 12, 2020. https://www.nei.nih.gov/learn-about-eye-health/resources-for-health-educators/eye-health-data-and-statistics/cataract-data-and-statistics
  2. Gollogly HE, Hodge DO, St. Sauver JL, Erie JC. Increasing incidence of cataract surgery: Population-based study. Journal of Cataract & Refractive Surgery. 2013;39(9):1383–1389. doi:10.1016/j.jcrs.2013.03.027
  3. Yamane S, Inoue M, Arakawa A, Kadonosono K. Sutureless 27-Gauge Needle–Guided Intrascleral Intraocular Lens Implantation with Lamellar Scleral Dissection. Ophthalmology. 2014;121(1):61-66. doi:10.1016/j.ophtha.2013.08.043
  4. Narang P, Agarwal A. Glued intrascleral haptic fixation of an intraocular lens. Indian J Ophthalmol. 2017;65(12):1370-1380. doi:10.4103/ijo.IJO_643_17
  5. Mohan S, John B, Rajan M, Malkani H, Nagalekshmi SV, Singh S. Glued intraocular lens implantation for eyes with inadequate capsular support: Analysis of the postoperative visual outcome. Indian J Ophthalmol. 2017;65(6):472-476. doi:10.4103/ijo.IJO_375_16
  6. Kumar S, Singh S, Singh G, Rajwade NS, Bhalerao SA, Singh V. Visual outcome and complications of various techniques of secondary intraocular lens. Oman Journal of Ophthalmology. 2017;10(3):198. doi:10.4103/ojo.OJO_134_2016
  7. Maheshwari R, Vaishnavi T, Revanasiddappa I, Joseph J, Kalikivayi V, Cherian Jacob S. Safety and efficacy of trans-scleral glued intraocular lens implantation. Annals of Eye Science. 2017;2(7):54.
  8. Hirashima DE, Soriano ES, Meirelles RL, Alberti GN, Nosé W. Outcomes of iris-claw anterior chamber versus iris-fixated foldable intraocular lens in subluxated lens secondary to Marfan syndrome. Ophthalmology. 2010;117(8):1479-1485. doi:10.1016/j.ophtha.2009.12.043
  9. Marianelli BF, Mendes TS, de Almeida Manzano RP, Garcia PN, Teixeira IC. Observational study of intraocular lens tilt in sutureless intrascleral fixation versus standard transscleral suture fixation determined by ultrasound biomicroscopy. International Journal of Retina and Vitreous. 2019;5(1):33. doi:10.1186/s40942-019-0182-y

Project Title: A longitudinal comparative study on retinitis pigmentosa patients with or without glaucoma and potential effects on optical coherence tomography, visual field examination, and medical intervention

Faculty Mentor: Jinghua Chen 
Email: jinghuachen@ufl.edu 

Student: Richard Artola
Email: richard.artola@ufl.edu  

Research Project Description:

Retinitis pigmentosa (RP) is a group of inherited disorders that result in a progressive loss of vision, even to the point of blindness. Specifically, it is the degeneration of photoreceptor cells of the retina and there is no cure. According to previous research, patients with retinitis pigmentosa are also more likely to develop both angle-closure and open-angle glaucoma (Ko et al., 2014. Eballe et al., 2010. Badeeb et al., 1993, Peng et al., 1990.). While retinal disorders and glaucoma have two seemingly different mechanisms, both can ultimately result in loss of vision. Currently, it is not known if there are any genetic mutations common to both diseases that can cause patients to be increasingly vulnerable.

The significance of these comorbidities on patient prognosis has not been investigated to our knowledge. Most likely, there is significant worsening of vision, especially with poor intraocular pressure control. While the two diseases are variably different, it is possible that both diseases result in a synergistic effect on vascular flow and poor perfusion of the retina. Previous research has shown that both diseases independently affect choroidal circulation. However, to what extent do these diagnoses combine to affect vision and does poor IOP control lead to even worse outcomes in these unique patients? If having both diagnoses results in a high risk of poor prognosis, it means these patients are significantly vulnerable and should be targeted for additional educational outreach.

It is hypothesized that in our patient population we will report an increased association between open-angle/acute-angle glaucoma and retinitis pigmentosa. Furthermore, comparing this subset of patients with control patients, we should see significant worsening of vision and changes in optical coherence tomography (OCT) biomarkers in the former group (Liu et al. 2016). For example, according to a 2007 study by Walia et al., researchers concluded that RP itself lead to thinner RNFL without evidence of glaucomatous damage to the optic disc.
We also aim to investigate the effect of poor IOP control among these patients through comparison of average IOP or need for intraocular procedures. Both comorbidities have been shown to be associated together in the past and both can result in severe vision loss. The rationale is that both diseases have a combined effect on perfusion and vascular flow of the retina, resulting in increased degeneration and patterns evidenced on the OCT (Schmidt et al., 2001. Langham and Kramer, 1990. Dollery et al., 1968).

The aim of this research is to investigate the incidence of open-angle and narrow-angle glaucoma in patients with retinitis pigmentosa, potential gene mutations common to both diseases, and the impact of comorbid glaucoma on their prognosis. Outcomes will be measured through observed changes in best corrected visual acuity, Humphrey and Goldmann visual field examinations, macula and RNFL OCT data, electroretinography (ERG) measurements, average IOP baseline, and patient treatment/responses.

References:

  1. Badeeb, O., Trope, G., & Musarella, M. (1993). Primary angle closure glaucoma and retinitis pigmentosa. Acta ophthalmologica, 71(6), 727-732.
  2. Dollery, C. T., Henkind, P., Kohner, E. M., & Paterson, J. W. (1968). Effect of raised intraocular pressure on the retinal and choroidal circulation. Investigative Ophthalmology & Visual Science, 7(2), 191-198.
  3. Eballe, A. O., Koki, G., Emche, C. B., Bella, L. A., Kouam, J. M., & Melong, J. (2010). Blindness and visual impairment in retinitis pigmentosa: a Cameroonian hospital-based study. Clinical ophthalmology (Auckland, NZ), 4, 661.
  4. Ko, Y. C., Liu, C. J., Hwang, D. K., Chen, T. J., & Liu, C. J. (2014). Increased risk of acute angle closure in retinitis pigmentosa: a population-based case-control study. PloS one, 9(9).
  5. Langham, M. E., & Kramer, T. (1990). Decreased choroidal blood flow associated with retinitis pigmentosa. Eye, 4(2), 374-381.
  6. Liu, G., Liu, X., Li, H., Du, Q., & Wang, F. (2016). Optical coherence tomographic analysis of retina in retinitis pigmentosa patients. Ophthalmic research, 56(3), 111-122.
  7. Peng T, Wu L, Zhou W. Retinitis pigmentosa associated with glaucoma–clinical analysis. Yan ke xue bao (2016). 1990 Jun;6(1-2):17-19
  8. Schmidt, K. G., Pillunat, L. E., Kohler, K., & Flammer, J. (2001). Ocular pulse amplitude is reduced in patients with advanced retinitis pigmentosa. British Journal of Ophthalmology, 85(6), 678-682.
  9. Walia, S., Fishman, G. A., Edward, D. P., & Lindeman, M. (2007). Retinal nerve fiber layer defects in RP patients. Investigative ophthalmology & visual science, 48(10), 4748-4752.

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