Comparative Analysis of Macular Choroidal Thickness in Pseudoexfoliative Glaucoma, Primary Open-Angle Glaucoma, and Healthy Controls

doi:10.21203/rs.3.rs-4999355/v1

Download PDF

Research Article

Comparative Analysis of Macular Choroidal Thickness in Pseudoexfoliative Glaucoma, Primary Open-Angle Glaucoma, and Healthy Controls

https://doi.org/10.21203/rs.3.rs-4999355/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Purpose

To compare macular choroidal thickness (CT) among eyes with pseudoexfoliative glaucoma (PEG), primary open-angle glaucoma (POAG), and healthy control eyes.

Methods

The study compared macular CT among 60 eyes in each of PEG (Group A), POAG (Group B) and age and sex matched healthy controls (Group C). Key inclusion criteria were age ≥ 18 years, BCVA ≥ 20/40 and IOP ≥ 21 mmHg. Exclusion criteria were axial length ≥ 25 mm, neurological disorders, retinal or choroidal diseases. Enhanced-depth spectral domain optical coherence tomography (EDI- SD OCT) was used to measure the choroidal thicknesses across all zones of Early Treatment Diabetic Retinopathy Study (ETDRS) grid of all subjects.

Results

The average macular CT showed a significant decrease in PEG compared to controls (p = 0.02). CT was also thinner in PEG in the nasal inner (p = 0.03), superior inner (p = 0.01), inferior inner (p = 0.01), superior outer (p = 0.01), and temporal outer (p = 0.03) subfields of the macula compared to controls. In POAG, thinner choroid was observed in the central (p = 0.02), nasal inner (p = 0.02), and superior inner (p = 0.02) subfields compared to controls. When comparing PEG to POAG, thinner choroid was seen in the inferior inner subfield of the macula in PEG (p = 0.01).

Conclusion

The significant thinning observed in various macular subfields of PEG and POAG groups, underscores the importance of evaluating CT alterations in glaucoma.

Choroidal thickness

Pseudoexfoliative glaucoma

Primary open angle glaucoma

Pseudoexfoliation syndrome (PEX) represents an age-related disorder characterized by abnormal elastosis and the deposition of microfibril material throughout the extracellular matrix, affecting ocular tissue systematically. This material accumulates on various ocular structures, including the lens capsule, zonular fibres, iris, trabeculum, and conjunctiva. PEX stands out as the most widely acknowledged independent risk factor for glaucoma. Roughly half of patients with PEX develop secondary open-angle glaucoma (OAG) over their lifetime, with pseudoexfoliative glaucoma (PEG) constituting 25% of OAG cases globally [1]. The deposition of pseudoexfoliative material within the trabecular meshwork and the obstruction of Schlemm’s canal consequently leads to elevated intraocular pressure (IOP) and the development of PEG. Notably, exfoliative material is not confined to the anterior segment tissues of the eyes, such as the corneal endothelium, lens surface, and trabecular meshwork, but may also impact posterior segment tissues, including the posterior ciliary arteries, vortex veins, and central retinal vessels [2].

The choroid has the highest perfusion rate of all blood vessels in the human body. Due to its crucial role in ocular blood flow regulation, it significantly influences the development and progression of glaucoma [3]. Choroidal thickness (CT) correlates directly with its blood flow, and measurements obtained through Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) offer valuable insights into choroidal blood flow velocity. Previous studies have investigated the impact of choroidal blood supply on glaucoma development [4, 5].

While the posterior ciliary arteries predominantly supply the laminar region of the optic nerve head (ONH), the prelaminar region and the surface of the optic disc rely primarily on peripapillary choroidal circulation. Hence, choroidal circulation is proposed to contribute to the pathophysiology of glaucomatous optic neuropathy.

Currently, research on macular CT in eyes with pseudoexfoliative glaucoma (PEG) and primary open-angle glaucoma (POAG) is limited and contentious. The question of whether exfoliative substances can disrupt ocular blood flow remains unresolved. Recent evidence suggests that greater intraocular pressure (IOP) fluctuation alone may not entirely account for the poorer prognosis of PEG compared to POAG [6]. This uncertainty in the pathogenesis of PEG resembles a puzzle with missing pieces. In this study, our objective was to explore the role of the macular choroid as a potential missing piece by comparing macular CT in eyes with PEG, POAG, and healthy control eyes, using EDI SD-OCT.

This comparative study was conducted at the outpatient department of a tertiary eye care hospital to compare 60 eyes with PEG (Group A) and 60 eyes with POAG (Group B) against 60 eyes of age- and sex-matched healthy controls (Group C). The study adhered strictly to the tenets of the Declaration of Helsinki and received approval from the institutional ethics committee. Prior to enrolment, written informed consent was obtained from all participants.

PEG was defined as the presence of exfoliation material on the pupillary margin and/or anterior capsule of the lens, IOP ≥ 21 mm Hg (at the time of diagnosis without antiglaucoma drugs), and evidence of glaucomatous optic nerve damage accompanied by visual field defects. In cases of unilateral PEG, only the affected eye was included, whereas in bilateral symmetric or asymmetric cases, either the right eye or the more prominently affected eye was selected. Cases of secondary open-angle glaucoma due to other causes were meticulously ruled out. POAG was defined by open angles, IOP ≥ 21 mm Hg, and the presence of glaucomatous optic nerve damage alongside visual field defects.

Key inclusion criteria encompassed subjects aged 18 years or older, with best-corrected visual acuity (BCVA) of ≥ 20/40 and IOP ≥ 21 mmHg. Exclusion criteria included subjects under 18 years of age, those with a spherical equivalent beyond ± 6 dioptres, axial length exceeding 25 mm, individuals with neurological disorders potentially influencing visual field defects, and those with retinal or choroidal diseases. Additionally, subjects with a history of previous ocular surgery or laser procedures, chronic diseases such as diabetes, hypertension, renal disorders, endocrine disorders, pregnancy, chronic medication usage likely to affect choroidal thickness, or a history of smoking were excluded. Media opacity that could potentially affect signal strength in SD-OCT imaging was also grounds for exclusion.

A comprehensive ocular examination was conducted on all subjects, including measurement of BCVA, slit-lamp biomicroscopy, Goldmann applanation tonometry, gonioscopy, fundus examination after mydriasis, central corneal thickness (CCT) measurement by pachymetry, and standard white-on-white visual field testing using the 30 − 2 Swedish Interactive Threshold Algorithm.

CT was measured using EDI mode of SD-OCT (Spectralis, HEYEX software 6.0, Heidelberg Engineering, Heidelberg, Jena, Germany). A macular (30°x25°) volume scan was performed, measuring CT from the outer portion of the hyperreflective line corresponding to the retinal pigment epithelium to the junction between the large vessel layer of the choroid and the sclera across all zones of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, which included circles of diameters 1 mm, 3 mm, and 6 mm [Fig. 1]. Imaging was consistently conducted between 0900 h and 1100 h in the morning to minimize potential diurnal variations.

Statistical analysis was carried out using Statistical Package for Social Sciences version 15.0 (SPSS, Inc., Chicago, IL). Differences in CT among the three groups were assessed using unpaired t-tests, with significance set at a p-value less than 0.05.

The study compared 60 eyes with PEG (Group A) and 60 eyes with POAG (Group B) with 60 healthy control eyes (Group C). All three groups showed similar mean ages (Group A: 66.46 ± 6.25 years; Group B: 66.88 ± 5.43 years; Group C: 64.33 ± 6.88 years) and comparable sex ratios [Table 1]. Additionally, refractive spherical equivalent, IOP, CCT, axial length, and cup-to-disc ratio were similar between the PEG and POAG groups [Table 1]. The visual field defects were comparable between the cases of PEG and POAG [Table 2].

Table 1

Baseline features of eyes with pseudoexfoliative glaucoma (group A), primary open angle glaucoma (group B) and control eyes (Group C)
Baseline features	Group A (N = 60 eyes)	Group B (N = 60 eyes)	Group C (N = 60 eyes)	P - value
Age (Years ± SD)	66.46 ± 6.25	66.88 ± 5.43	64.33 ± 6.88	0.06
Male : Female	37 : 23	33 : 27	33 : 27	-
CCT (µm ± SD)	508.9 ± 10.38	505.1 ± 11.21	502.8 ± 11.37	*0.01
Refractive Error (D ± SD)	0.22 ± 1.63	-0.05 ± 1.95	-0.11 ± 1.8	0.57
Axial length (mm ± SD)	23.21 ± 0.60	23.09 ± 0.89	23.19 ± 0.69	0.64
IOP (mm of Hg ± SD)	19.36 ± 2.04	18.28 ± 3.76	16.66 ± 2.66	< 0.001
Cup disc ratio (Mean ± SD)	0.79 ± 0.12	0.77 ± 0.13	0.37 ± 0.10	0

SD, standard deviation; CCT, Central corneal thickness; D, Dioptres; IOP, Intraocular pressure

Table 2

Visual field defects in eyes with Pseudoexfoliative glaucoma (Group A) and Primary open angle glaucoma (Group B)
Visual field defects	Group A (N = 60)	Group B (N = 60)	P- value
Paracentral scotoma	26 (43.3%)	29 (48.3%)	0.7
Nasal step	15 (25%)	17 (28.3%)	0.7
Siedel’s scotoma	10 (16.6%)	11 (18.3%)	0.8
Arcuate scotoma	6 (1.6%)	2 (3.3%)	0.2
Ring scotoma	3 (5%)	1 (1.6%)	0.4

The average macular CT exhibited a statistically significant decrease in PEG compared to controls (p = 0.02) [Fig. 2] [Table 3]. Conversely, although the average macular CT was lower in POAG compared to controls, this disparity did not reach statistical significance (p = 0.12). Moreover, the difference in average macular CT between PEG and POAG groups was not statistically significant (p = 0.54).

Table 3

Choroidal thickness in macular subfields of eyes with pseudoexfoliative glaucoma (group A), primary open angle glaucoma (group B) and control eyes (Group C)
Macular choroidal thickness parameter	Group A (µm ± SD) N = 60	Group B (µm ± SD) N = 60	Group C (µm ± SD) N = 60	P- value (A vs C)	P- value (B vs C)	P- value (A vs B)
CSM	277.07 ± 51.33	272.23 ± 53.69	292.62 ± 40.30	0.07	*0.02	0.6
NIM	229.60 ± 37.65	225.73 ± 45.51	248.82 ± 59.53	*0.03	*0.02	0.6
SIM	282.05 ± 53.01	284.30 ± 51.48	304.72 ± 43.80	*0.01	*0.02	0.8
TIM	255.22 ± 46.40	266.43 ± 52.11	268.55 ± 31.38	0.06	0.7	0.2
IIM	245.32 ± 46.29	267.53 ± 51.20	264.35 ± 40.25	*0.01	0.7	*0.01
NOM	202.75 ± 48.00	207.8 ± 48.59	217.33 ± 43.84	0.08	0.26	0.56
SOM	271.82 ± 52.36	275.73 ± 54.80	293.62 ± 41.84	*0.01	0.05	0.67
TOM	251.53 ± 56.46	261.82 ± 52.89	271.65 ± 46.50	*0.03	0.28	0.3
IOM	239.22 ± 87.13	252.83 ± 56.46	258.62 ± 50.25	0.14	0.55	0.31
AM	253.05 ± 46.66	258.60 ± 51.85	272.25 ± 43.37	*0.02	0.12	0.54
* Statistically significant; CSM, central subfield macula; NIM, nasal inner macula; SIM, superior inner macula; TIM, temporal inner macula; IIM, inferior inner macula; NOM, nasal outer macula; SOM, superior outer macula, TOM, temporal outer macula; IOM, inferior outer macula; AM, average macula

We observed significantly thinner choroid in PEG in the nasal inner (p = 0.03), superior inner (p = 0.01), inferior inner (p = 0.01), superior outer (p = 0.01), and temporal outer (p = 0.03) subfields of the macula compared to controls [Table 3] [Fig. 2]. Although all other subfields of the macula also exhibited comparatively thinner choroid in Group A, the differences were not statistically significant (P > 0.05).

In POAG, significantly thinner choroid was observed in the central (p = 0.02), nasal inner (p = 0.02), and superior inner (p = 0.02) subfields compared to controls [Table 3] [Fig. 2]. Except for the inferior inner macula, all other subfields of the macula also exhibited comparatively thinner choroid in POAG, but the differences were not statistically significant (P > 0.05).

When comparing PEG to POAG, significantly thinner choroid was seen in the inferior inner subfield of the macula in PEG (p = 0.01). Except for the central and nasal inner subfields, all other subfields of the macula also exhibited comparatively thinner choroid in PEG, although the differences were not statistically significant (P > 0.05). The central and nasal inner subfields of the macula had a thinner CT in POAG, but the differences were not statistically significant.

This study provides valuable insights into the CT differences among patients with PEG, POAG, and healthy controls. Our findings reveal significant variations in macular CT across these groups.

Cennamo et al. found that individuals with POAG exhibited thicker macular CT measured by SD-OCT compared to healthy subjects [7]. Egrilmez et al discovered that patients with PEX had thinner macular CT compared to both POAG patients and healthy controls [8]. Moghimi et al reported significantly lower CT and volumes in several macular subfields among PEX patients compared to healthy individuals, although no notable differences were observed after adjusting for demographic factors [6]. Koz et al. identified signs of glaucomatous optic nerve damage in PEX patients despite normal intraocular pressure (IOP), suggesting that the presence of the highest IOP and greatest IOP fluctuation in PEX eyes may be important factors in the progression of glaucoma and that the presence of exfoliative material may be an independent risk factor for optic nerve damage [9]. Prior studies revealed that the macular CT of eyes affected by PEG was thinner than that of fellow eyes without PEG [10, 11]. They also noted a progressive thinning of the choroid with advancing PEX, hinting at vascular factors beyond IOP as potential contributors to PEG, possibly linked to hemodynamic alterations induced by exfoliative material deposition on vascular structures [12].

The significantly lower average macular CT observed in our study, in PEG compared to controls, underscores the potential role of choroidal alterations in the pathogenesis of PEG. This finding aligns with previous studies suggesting a link between CT and glaucomatous optic neuropathy. The reduction in CT could reflect compromised ocular perfusion in PEG, contributing to optic nerve damage and visual field defects.

In contrast, while we observed a trend towards decreased average macular CT in POAG compared to controls, this difference did not attain statistical significance. This discrepancy might stem from variations in disease mechanisms and severity between PEG and POAG. Additionally, factors such as disease duration and treatment regimens could influence CT alterations differently in these two glaucoma subtypes.

The lack of a significant difference in average macular CT between PEG and POAG groups suggests comparable choroidal changes despite distinct underlying etiologies. However, the trend towards thinner choroid in PEG merits further investigation to elucidate its clinical implications and potential therapeutic targets.

Our analysis of sectoral CT revealed specific subfield differences between PEG, POAG, and controls. The significant thinning observed in various macular subfields of PEG and POAG groups, particularly in the nasal inner, superior inner, and inferior inner subfields, underscores the regional variations in choroidal alterations associated with glaucomatous optic neuropathy. These findings highlight the importance of evaluating CT changes in specific macular regions to better understand the localized impact of glaucoma on choroidal vascular dynamics.

Despite the novel insights provided by this study, several limitations warrant consideration. The cross-sectional design precludes establishing causality, and longitudinal studies are needed to elucidate the temporal relationship between choroidal changes and glaucomatous progression. Additionally, our sample size might limit the generalizability of findings, and future studies with larger cohorts are warranted to validate our results.

In conclusion, our findings underscore the importance of evaluating CT alterations in glaucoma and suggest potential differences in choroidal vascular dynamics between PEG and POAG. Further research is warranted to elucidate the mechanistic underpinnings of choroidal changes in glaucoma and their implications for disease management and prognosis.

Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing Interests: The authors have no relevant financial or non-financial interests to disclose.

Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ananya Chatterjee, Vikas Ambiya. The first draft of the manuscript was written by Ananya Chatterjee and Vikas Ambiya. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.”

Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional ethical committee of Armed Forces Medical College, Pune (IEC/Oph/2022 dated 25 August 2022).

Consent to participate: Informed consent was obtained from all individual participants included in the study.

Consent to publish: Not applicable.

Acknowledgement: Nil

Conflicting Interest (If present, give more details): The Authors declare that there is no conflict of interest.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval: By Institutional Ethical Committee

Data availability statement: The data is available with the authors.

Presentation at a meeting: Nil

Source(s) of support: Nil

The manuscript has been read and approved by all the authors, the requirements for

authorship as stated earlier in this document have been met, and each author believes that the manuscript represents honest work.

Ritch R, Schlötzer-Schrehardt U (2001) Exfoliation syndrome. Surv Ophthalmol 45:265–315.
Bayhan HA, Bayhan SA, Can İ (2016) Evaluation of the macular choroidal thickness using spectral optical coherence tomography in pseudoexfoliation glaucoma. J Glaucoma 25:184–187.
Dayanir V, Topaloğlu A, Ozsunar Y, Keceli M, Okyay P, Harris A (2009) Orbital blood flow parameters in unilateral pseudoexfoliation syndrome. Int Ophthalmol 29:27–32.
Mwanza JC, Sayyad FE, Budenz DL (2012) Choroidal thickness in unilateral advanced glaucoma. Invest Ophthalmol Vis Sci 53:6695–6701.
Zhang Z, Yu M, Wang F, Dai Y, Wu Z (2016) Choroidal thickness and open-angle glaucoma: A meta-analysis and systematic review. J Glaucoma 25:e446–454.
Moghimi S, Mazloumi M, Johari MK, Fard MA, Chen R, Weinreb R, et al. (2017) Comparison of macular choroidal thickness in patients with pseudoexfoliation syndrome to normal control subjects with enhanced depth SD-OCT imaging. J Curr Ophthalmol 29:258–263.
Cennamo G, Finelli M, Iaccarino G, de Crecchio G, Cennamo G (2012) Choroidal thickness in open-angle glaucoma measured by spectral-domain scanning laser ophthalmoscopy/optical coherence tomography. Ophthalmologica 228:47–52.
Egrilmez ED, Ugurlu SK, Atik SS, Guven YZ (2019) The effect of pseudoexfoliation syndrome on choroidal thickness in open-angle glaucoma. Arq Bras Oftalmol 82:400–406.
Koz OG, Turkcu MF, Yarangumeli A, Koz C, Kural G (2009) Normotensive glaucoma and risk factors in normotensive eyes with pseudoexfoliation syndrome. J Glaucoma 18:684–688.
Li F, Shang Q, Tang G, Zhang H, Yan X, Ma L, et al. (2020) Analysis of peripapillary and macular choroidal thickness in eyes with pseudoexfoliative glaucoma and fellow eyes. J Ophthalmol 2020:9634543.
Li F, Ma L, Geng Y, Yan X, Zhang H, Tang G, et al. (2020) Comparison of macular choroidal thickness and volume between pseudoexfoliative glaucoma and pseudoexfoliative syndrome. J Ophthalmol 2020:8886398.
Lin Z, Huang S, Huang P, Guo L, Shen X, Zhong Y (2017) The diagnostic use of choroidal thickness analysis and its correlation with visual field indices in glaucoma using spectral domain optical coherence tomography. PLOS ONE 12:e0189376.
Statements & Declarations

No competing interests reported.

Download PDF

Editor assigned by journal
30 Aug, 2024
Submission checks completed at journal
30 Aug, 2024
First submitted to journal
29 Aug, 2024

You are reading this latest preprint version

Comparative Analysis of Macular Choroidal Thickness in Pseudoexfoliative Glaucoma, Primary Open-Angle Glaucoma, and Healthy Controls

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Methods

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1