Dr.Zia Sultan Pradhan

Dr.Sujani Shroff, Dr. POORNACHANDRA B., Dr.Harsha Rao

Semi Finals

Abstract

Although there is an established association between primary open-angle glaucoma (POAG) and retinitis pigmentosa (RP), little is known about primary angle-closure glaucoma (PACG). Additionally, identification of glaucomatous damage in RP is challenging as both cause RNFL thinning and field loss. This study aimed to determine the prevalence of PACG in RP patients and to identify biomarkers of glaucomatous damage in RP.

A retrospective chart review of 618 RP patients revealed 1.3% had POAG and 2.3% had PACG. In RP patients >40 years, prevalence of PACG was higher (3.8%) than in the general population (0.8%). Macular OCT scans of 21 eyes of RP with glaucoma were compared to matched RP controls without glaucoma. Though, total retinal thickness was similar between the groups, the perifoveal ganglion cell layer (GCC) was significantly thinner in RP patients with glaucoma.

Therefore, gonioscopy is warranted in RP patients. GCC thinning is a potential biomarker of glaucomatous damage in RP.

Full Text

Glaucoma in patients with retinitis pigmentosa

INTRODUCTION:

There is a well-established association between Retinitis Pigmentosa (RP) and glaucoma. Western literature has shown that 2-12% of RP patients have primary open-angle glaucoma (POAG). [1] However, there is scant literature on the association between primary angle closure disease (PACD) and RP. [1-3] Also, the identification of glaucomatous damage in these RP patients is challenging as both diseases cause RNFL thinning on OCT and progressive peripheral visual field loss.
Glaucoma is a disease of retinal ganglion cell apoptosis and OCT of the macula has shown thinning of the ganglion cell layer in even early glaucoma. In contrast, RP is a disease of photoreceptor degeneration and predominantly shows OCT changes in the outer retinal layer of the macula. Therefore, our hypothesis was that in eyes with both RP and glaucoma, the inner retinal layers of macula on Spectral Domain- OCT imaging will be thinner when compared to eyes with RP alone.The aim of the present study was to determine the prevalence of PACD in patients with RP. Additionally, we compared the thickness of different retinal layers on macular OCT in eyes of patients having both RP and glaucoma with those of RP alone.

METHODS:
This was a retrospective review of the electronic medical records of all patients over the age of 18 years with RP attending a Genetics Eye Clinic between April 2012 to June 2019. The study was performed in compliance with the Declaration of Helsinki and was approved by the Institutional Review Board and Ethics Committee.
All patients attending the Genetics Eye Clinic underwent a thorough medical history, family history and pedigree charting and complete ocular examination including vision, refraction, slit-lamp examination, intraocular pressure (IOP) measurement, and dilated fundus examination with a 90D lens. All patients attending the Genetics eye clinic also underwent a macular SD-OCT examination (Spectralis, Heidelberg Engineering, Germany) and visual fields examination (Humphrey Field Analyzer II, model 720i, Carl Zeiss Meditec, Inc. Dublin, CA, USA) when possible. The demographic data (age, gender, presence of systemic illnesses like diabetes mellitus and hypertension, refractive status, lens status, IOP) of all RP patients was retrieved. RP was defined based on clinical fundus appearance (waxy disc pallor, bony spicules, attenuation of blood vessels, etc) and confirmed on ERG in case of atypical fundus picture. All patients with a shallow anterior chamber, IOP greater than 21 mm Hg or cup:disc ratio >0.6 were referred to the glaucoma department for the opinion of a glaucoma specialist. Here, additional IOP measurements, gonioscopy using a 4 mirror goniolens, and an optic disc evaluation was performed. This supplementary data, as well as information regarding glaucoma treatment (medications, lasers or surgery) was also included for analysis. Other details collected were type of RP and mode of inheritance. Patients with retinal dystrophy other than RP and patients under 18 years of age (as they may not co-operate for a complete eye examination) were excluded.
The following definitions were used to classify patients referred to the glaucoma clinic:
Primary angle closure suspect: >180 degrees of iridotrabecular contact (ITC), IOP <21mmHg, and cup:disc ratio ≤0.6. Primary angle closure: >180 degrees of ITC with peripheral anterior synechiae (PAS) or IOP >21mmHg, and cup:disc ratio ≤0.6.

Primary angle closure glaucoma: >180 degrees of ITC, IOP >21mmHg, and cup:disc ratio ≥0.7. Primary open-angle glaucoma: Open angles, IOP > 21 mmHg, and cup:disc ratio ≥0.7. Secondary glaucomas: IOP > 21 mmHg with an identifiable secondary cause.

In additional to the prevalence data, the macular SD-OCT of cases (RP with glaucoma) were compared with controls (RP alone). Cases were defined as eyes with RP which had an IOP >21 mmHg on Goldmann applanation tonometry with or without glaucomatous changes. Controls were RP patients with IOP ≤ 21mmHg. Cases and controls were matched for visual acuity and central foveal thickness. For this part of the analysis, the exclusion criteria were eyes with previous ocular surgery (except uncomplicated cataract surgery), cystoid macular edema, epiretinal membrane, any form of maculopathy and poor signal strength of OCT scans (<20).
The segmentation software on the Spectralis OCT was used to study each layer at the macula. This divides the macula into 4 perifoveal and 4 parafoveal sectors around the fovea (ETDRS grid). This software can analyse individual layers at the macula and give the thickness and volume of each sector. It also provides the thickness of the inner retinal layer (IRL) measured from the internal limiting membrane (ILM) to the external limiting membrane (ELM). The outer retinal layer (ORL) is measured from the ELM to the Bruch’s membrane.
Statistical analysis was performed using Stata version 14.2 (StataCorp, College Station, Tx). Mean with standard deviation (SD) was calculated for continuous variables and frequency with percentage (%) were tabulated for categorical variables. The t-test was used to compare the retinal thickness between the groups. A p value ≤0.05 was considered statistically significant.

RESULTS:
The electronic medical records of 618 RP patients were analysed. Based on the definitions of glaucoma, 1.3% had POAG and 2.3% had primary angle closure glaucoma (PACG). In RP patients over 40 years of age, the prevalence of PACG was 3.8%. In the analysis of macular OCT, 21 eyes of 13 patients with glaucoma and RP were included as the cases. These were compared with 26 control eyes of 24 RP patients with no evidence of glaucoma. The glaucomatous patients included 8 POAG and 13 PACG eyes. There was no significant difference in the age, gender, visual acuity or refraction between the cases and controls. The Median IOP was 13.5 (IQR 11.5,16.5) mmHg in the control groups and 24.0 (IQR 16,29) in the cases (p=0.018). Also, the cup: disc ratio was significantly higher in the cases (0.77 ± 0.19 vs 0.33 ± 0.13, p<0.0001). The visual field parameters (mean deviation and visual field index) were similar between the groups. The central foveal thickness was similar between the groups (259.9 ± 43.7 and 270.5 ± 49.7, p=0.44). There was no difference between the total retinal thickness of the 2 groups in any of the ETDRS sectors. The ganglion cell complex (GCC) layer of the inferior (70 ± 17 vs 83 ± 21) and nasal (84 ± 30 vs 101 ± 21) perifoveal sectors were significantly thinner (p<0.05) in the patients with RP and glaucoma compared to the controls. The outer retinal layers had a similar thickness in both groups.

DISCUSSION:
This study determined the prevalence of angle closure in an RP population. There is limited literature on the prevalence of angle closure disease and RP. [1-3] In the present study, the prevalence of PACG in RP patients over the age of 40 years was 3.8 % which is higher than the prevalence measured in population-based studies in India (0.8%). [4] This strong association between RP and PACG warrants a careful and thorough examination, including gonioscopy, in all patients with RP.

There is a lot of literature on the GCC thinning in glaucoma since retinal ganglion cells (RGCs) are the predominant cell affected in the disease. [5] Interestingly, studies have also shown GCC thinning in RP. [6] There are 2 main theories put forth to explain this finding. One is the photoreceptor degeneration causes reduced transsynaptic signals and secondary RGC loss. The other theory is that the reduced blood flow to the inner retinal layers causes RGC degeneration and GCC thinning. The literature on imaging in RP and glaucoma is sparse and this is the first study evaluating the retinal layers on macular SD-OCT in this cohort. We found that the GCC layer in the perifoveal regions is significantly thinner in eyes of RP patients with glaucoma despite the total retinal thickness being similar. Hence, the GCC may be a biomarker for glaucoma in eyes with RP and a detailed segmental assessment of these retinal layers should be performed in eyes with RP suspected of having glaucoma. Future longitudinal studies of these patients should be done to monitor progressive changes in the macula on SDOCT.

CONCLUSION
This study has shown that gonioscopy is warranted as part of the routine examination in RP patients. Eyes with RP and glaucoma have a thinner GCC layer in the perifoveal region. Hence, GCC thinning is a potential biomarker of glaucomatous damage in RP.

REFERENCES:
1. Badeeb O, Trope G, Musarella M. Primary angle closure glaucoma and RP. Acta Ophthalmological 1993; 71: 727-732.
2. Carlos a Omphroy. Sector Retinitis Pigmentosa and chronic angle closure glaucomabv: A new association. Ophthalmological, Basel 189: 12-20 (1984)
3. Ko Y-C, Liu C-J, Hwang D-K, Chen T-J, Liu CJ (2014) Increased Risk of Acute Angle Closure in Retinitis Pigmentosa: A Population-Based Case-Control Study. PLoS ONE 9(9): e107660. doi:10.1371/journal.pone.0107660
4. Ronnie George et al. Glaucoma in India: Estimated burden of disease. J Glaucoma 2010; 19:391–397)
5. Pazos et al. Diagnostic accuracy of SD OCT automated macular layers segmentation to discrimate normal and early glaucoma. Ophthalmology 2017; 124:1218-1228
6. Toto et al. Macular features in RP: Correlations among GCC thickness, capillary density and macular function. IOVS 2016; 57: 6360 – 6366