The Relationship Between Macular Pigment Optical Volume and Visual Function in Glaucoma Patients

Abstract

Purpose

This study aimed to investigate the relationships among visual field (VF) sensitivity, retinal structure, and macular pigment in glaucoma.

Methods

A total of 218 eyes from 121 patients diagnosed with primary open-angle glaucoma were included. VF sensitivity was assessed using the 10-2 test with the Humphrey Field Analyzer. Macular pigment optical volume (MPOV) was measured using the two-wavelength fundus autofluorescence method with SPECTRALIS optical coherence tomography (OCT). Additionally, ganglion cell complex (GCC) and nerve fiber layer (NFL) thickness were evaluated using OCT. The relationships among VF sensitivity, retinal structure, and MPOV were evaluated by matching the measurement areas of each test as closely as possible.

Results

The mean age of participants was 71.6 ± 10.8 years (49 males). MPOV showed no significant association with VF sensitivity in either the superior or inferior hemiretina (P = 0.75 and P = 0.42, respectively). MPOV was not significantly associated with GCC or NFL thickness in both the superior and inferior hemiretina (P > 0.05).

Conclusions

In glaucoma patients, MPOV was not associated with VF sensitivity, GCC, or NFL. These findings suggest no structural or functional association between MPOV and glaucomatous damage.

The human retina contains macular pigment (MP) consisting of three xanthophyll carotenoids: lutein, (3R,3′R,6′R)-lutein; zeaxanthin, (3R,3′R)-zeaxanthin; and meso-zeaxanthin, (3R,3′S; meso)-zeaxanthin.^1,2 The maximum absorption wavelengths of these xanthophyll carotenoids lie within the blue region of the visible light spectrum, and these carotenoids have strong antioxidant activity. MP is concentrated in the central area of the retina within a circle with a radius of approximately 3000 µm (from the fovea to the parafovea) and is mainly located in the inner layers of the retina. The fovea (foveola in anatomical terminology, approximately 350 µm in diameter) contains more zeaxanthin and meso-zeaxanthin, whereas more lutein is present in the peripheral regions.³ MP protects photoreceptor cells from light-induced damage through its filtering effect by absorbing blue light, its antioxidant properties, and its anti-inflammatory effects.⁴ Functionally, much MP improves contrast sensitivity and reduces glare disability.^5,6 Research on the relationships among lutein, zeaxanthin, MP, and age-related macular degeneration (AMD) has been actively conducted. After reports emerged on the association between lutein and zeaxanthin intake and AMD,⁷ it was found that patients with AMD have lower levels of MP compared to healthy individuals.^8,9 Furthermore, the intake of lutein and zeaxanthin supplements, which help increase MP,^10–12 can suppress the onset of AMD,¹³ although some studies have failed to prove it.

Glaucoma is a progressive neurodegenerative disease characterized by retinal ganglion cell death and loss of nerve fibers,¹⁴ leading to visual field (VF) deterioration. Structural changes, including axonal loss, underlie glaucomatous damage.^15–17 Glaucoma is the second leading cause of blindness worldwide, affecting over 60 million people.¹⁸ The pathogenesis of glaucoma is complex and is thought to involve factors such as physical damage to the optic nerve due to elevated intraocular pressure; however, oxidative stress is also considered to be one of the contributing factors. Several mechanisms have been proposed regarding the relationship between glaucoma and oxidative stress. Reactive oxygen species (ROS) generated by oxidative stress directly damage retinal ganglion cells (RGCs). ROS generated by circulatory disturbances can lead to excessive nitric oxide production, which in turn generates highly reactive oxidants such as peroxynitrite, causing further damage to RGCs. Oxidative stress also impairs mitochondrial function in neuronal cells, leading to reduced adenosine triphosphate (ATP) production. Additionally, oxidative stress contributes to dysfunction of the trabecular meshwork, impairing aqueous humor outflow. Considering the influence of oxidative stress, the intake of antioxidants and their potential role in preventing glaucoma progression have been studied. The intake of fruits and vegetables is associated with a reduced odds ratio for glaucoma, particularly in the early stages of glaucoma.^19,20 It has also been reported that the intake of vitamins A, B, and C, as well as carotenoids, lowers the odds ratio for glaucoma.²⁰ Much intake of fruits and vegetables increases macular pigment optical density (MPOD); therefore, the association between glaucoma and MPOD has been studied. Most of the studies have used heterochromatic flicker photometry (HFP) to measure MPOD. HFP is a subjective test that can measure MPOD at certain eccentricities. MPOD at 0.5° eccentricity from the foveal center (namely, near the edge of the fovea) was reported to be lower in glaucoma than in healthy individuals.^21,22 In healthy individuals, MPOD is reported to have a positive correlation with the thickness of the ganglion cell complex (GCC), which is comprised of the nerve fiber layer (NFL), ganglion cell layer, and inner plexiform layer,²³ and a similar correlation has been demonstrated in glaucoma.²⁴ In advanced glaucoma, the GCC is thinner, and MPOD values at 0.25°, 0.5°, and 1° eccentricities were reported to be lower than those in healthy individuals. However, the association between MPOD and VF sensitivity has not been verified. The Carotenoids in Age-Related Eye Disease Study (CAREDS),^22,24 which followed postmenopausal women over a 15-year period, showed that individuals with higher MPOD measured by HFP at baseline had greater GCC thickness 15 years later and a lower odds ratio for glaucoma. These findings suggest that MP may help prevent GCC thinning and play a protective role in the onset of glaucoma. In contrast, studies using the fundus autofluorescence method to measure MPOD have reported conflicting results, including that there were no differences in total pigment volume within 6° eccentricities²⁵ or in MPOD at 0.5°, 1°, and 2° eccentricities between glaucoma patients and healthy individuals.²⁶ The reasons for these discrepancies remain unclear, but variations in study methodologies may have contributed to the inconsistency; that is, some studies used HFP and others used the reflectometry method²⁷ or autofluorescence method. Furthermore, some studies have focused exclusively on elderly women (mean age, 80.4 years),²² but others have compared only fovea-involved versus non-involved glaucoma patients²⁸ or have had small sample sizes (N < 100).^21,26–29 Measurement inconsistencies were also evident in VF testing, where different protocols were used, including the Humphrey Field Analyzer (HFA 24-2 or 30-2 tests; ZEISS Medical Technology, Jena, Germany),^{21,22,24,25,27,28} Octopus G1 perimetry (Haag-Streit, Köniz, Switzerland),²⁶ and a limited 19-test-point approach within 10° of the fovea.²⁹ Furthermore, previous studies have not aligned retinal layer thickness and VF test measurements with MP distribution.

To address these limitations, the present study aimed to align the measurement areas of retinal layer thickness and VF sensitivity as closely as possible with MP distribution. This approach allowed for a more precise evaluation of the relationship between MP and glaucoma-related structural and functional changes.

Methods

This retrospective observational study was approved by the Research Ethics Committee of Seirei Hamamatsu General Hospital (#3497) and conducted in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants, allowing their clinical data to be stored in the hospital database and used for research purposes.

Participants

The study included 218 eyes from 121 patients diagnosed with primary open-angle glaucoma (POAG) who were followed up at the Department of Ophthalmology, Seirei Hamamatsu General Hospital, between December 2020 and 2022. POAG was diagnosed based on the following criteria: (1) the presence of characteristic glaucomatous changes in the optic nerve head (ONH), including a rim notch with a rim width ≦ 0.1 disc diameters or a vertical cup-to-disc ratio of >0.7 and/or a retinal nerve fiber layer defect extending from the ONH margin, diverging in an arcuate or wedge shape beyond a major retinal vessel; or (2) presence of glaucomatous VF defects consistent with ONH changes, fulfilling Anderson–Patell criteria.³⁰ Patients with systemic or ocular conditions that could affect ONH and VF assessment were excluded, and eyes with macular abnormalities such as epiretinal membrane, macular hole, AMD, and macular edema that might affect MPOD were also excluded. Because cataracts can also affect MPOD measurement,³¹ the study population was limited to those with clinically insignificant cataracts or eyes with intraocular lens implantation. All participants were at least 20 years old at the time of enrollment.

Measurement of the MPOD

MP was measured using the two-wavelength fundus autofluorescence method with SPECTRALIS optical coherence tomography (OCT; Heidelberg Engineering, Heidelberg, Germany). The measurements have been detailed in full elsewhere.³² This method can not only measure MPOD at certain eccentricities from the foveal center but also obtain spatial distribution of the pigments. All of the patients underwent MPOD measurement under mydriasis with 2.5% phenylephrine hydrochloride and 1% tropicamide.

In our previous studies, we set a reference point at 9° of eccentricity and reported the total volume of MPOD (macular pigment optical volume [MPOV]) within 9°. Therefore, we measured MPOV within 9° in the present glaucomatous eyes and compared MPOV in glaucoma with previous data of healthy individuals. Next, MPOV within 2.5° of eccentricity from the foveal center was calculated with a reference point at 10°. MPOV in the range from 2.5° to 10° was estimated by subtracting the MPOV within 2.5° from the MPOV within 10°, as this zone fits the area of VF testing and area of retinal thickness measurement by OCT. The average MPOV in the superior hemiretina (MPOV_sup) of the ring-shaped area was computed by adding the MPOV in the 45° sectors of the supranasal, superior, and supratemporal sectors. The average MPOV in the inferior hemiretina (MPOV_inf) was computed by adding MPOV from 45° sectors of the inferonasal, inferior, and inferotemporal sectors. The SPECTRALIS software was unable to separate the 45° temporal and nasal sectors into upper and lower halves; hence, the remaining sectors were not included in the calculations (Fig.). Similarly, the average MPOV in the superior/inferior hemiretina within 2.5° (MPOV_sup2.5/MPOV_inf2.5) was calculated.

Figure.

Schematic representation of the superior and inferior hemifields used for calculating retinal layer thickness, MPOV, and visual field. (Left) Macular pigment. The green circle represents a reference point at 10° of eccentricity, and the red circle has a radius of 2.5°. (Middle) Retinal thickness areas measured. (Right) Visual field areas measured. Above and below the fovea, the measurement areas for MP, retinal layer thickness, and VF were aligned as closely as possible.

VF Measurement

Swedish interactive thresholding algorithm (SITA) standard measurements were obtained using the HFA 10-2 test and standard Goldmann III stimulus size. The analysis employed only a dependable VF fixation loss rate of <20% and false-positive rate of <15%, as recommended by the manufacturer. The average VF sensitivities corresponding to MPOV_sup and MPOV_inf were determined (VF_sup and VF_inf, respectively). However, because center 4 test points (X and Y coordinates = ±1°) reside within 2.5° from the fovea even with the macular GCC displacement (between 1.2° and 2.07°),^33–36 these test points were removed from the analysis.

Retinal Layer Thickness Measurements

The RS-3000 OCT (NIDEK Co., Ltd., Aichi, Japan) was used to measure the thickness of the retinal layers (GCC, NFL, and photoreceptor [PhR]). Measurement was conducted under mydriasis with the same regimen. All scans were performed using the raster scan procedure for 30° of viewing angle (128 × 512 pixels), with data from the middle 81 mm² used in the analysis. The current analysis includes data with a signal strength score of >7. Images that were indistinct due to eye movements or involuntary blinking were captured again or carefully discarded. Furthermore, all of the borders were examined, and eyes with segmentation mistakes were excluded from the experiment. For statistical analysis, the data from the left eye were mirror-imaged with those from the right eye.

The average thicknesses of GCC, NFL, and PhR corresponding to MPOV_sup and MPOV_inf were computed (GCC_sup, GCC_inf, NFL_sup, NFL_inf, PhR_sup, and PhR_inf, respectively). The PhR thickness was employed in the present study, following a recent report that highlighted the benefit of integrating this layer when assessing the structure–function link in glaucoma; it is not involved in the mechanism of glaucoma but is a useful representation of interindividual differences in retinal layer thicknesses.³⁷

Axial Length Measurement

A well-trained examiner evaluated the axial length (AL) of all patients using the IOLMaster 4 (Carl Zeiss Meditec, Jena, Germany).

Statistical Analyses

Using a linear mixed model, we evaluated the relationship between VF_sup and the values of GCC_inf, NFL_inf, PhR_inf, MPOV_inf, AL, and age. The linear mixed model was modified for the hierarchical structure of the data (each eye was nested to each patient), with measurements aggregated among patients to reduce any bias derived from the nested structure. Similarly, the relationship between VF_inf and the values of GCC_sup, NFL_sup, PhR_sup, MPOV_sup, AL, and age were studied. The relationships between MPOV_sup and the values of GCC_inf, NFL_inf, PhR_inf, AL, and age were then studied, with AL and age serving as covariates. A similar analysis was performed for MPOV_inf and the values of GCC_sup, NFL_sup, PhR_sup, AL, and age. Moreover, the relationships between VF_sup/inf and the values of GCC_inf/sup, NFL_inf/sup, PhR_inf/sup, MPOV_inf/sup2.5, AL, and age were also investigated. Statistical significance was set at P < 0.05. All analyses were performed using R 3.5.2 (The R Foundation for Statistical Computing, Vienna, Austria).

Results

Table 1 shows the patients’ characteristics. Table 2 shows the relationships between MPOV within 10° eccentricity and age, AL, and sex. MP levels were higher in older individuals, and inversely associated with axial length (P = 0.020), with no significant association with sex. Table 3 shows the relationships between the mean MPOV in a ring-shaped area between 2.5° and 10° eccentricity and GCC, NGFL, PhR, AL, and age. Here. as well, MPOVs showed a positive correlation with age, but no correlation was observed with other factors.

Table 1.

Demographics of the Validation Dataset

Parameter	Value
Age (y), mean ± SD	71.6 ± 10.8
Sex (male/female), n	49/72
Eyes (right/left), n	110/108
AL (mm), mean ± SD	24.9 ± 1.8
VFsup (dB), mean ± SD	20.6 ± 11.2
VFinf (dB), mean ± SD	25.7 ± 8.6
GCCsup (µm), mean ± SD	47.5 ± 10.0
GCCinf (µm), mean ± SD	47.8 ± 9.9
NFLsup (µm), mean ± SD	28.0 ± 8.5
NFLinf (µm), mean ± SD	27.8 ± 8.5
PhRsup (µm), mean ± SD	66.6 ± 3.9
PhRinf (µm), mean ± SD	66.7 ± 4.0
MPOV within 2.5°, mean ± SD	1,921.3 ± 634.3
MPOV in a ring-shaped area between 2.5° and 10°, mean ± SD	20,013.6 ± 7,070.2
MPOV within 9°, mean ± SD	19,187.2 ± 6,700.2
MPOV within 10°, mean ± SD	21,934.9 ± 7,335.1
MPOVsup, mean ± SD	5,997.7 ± 2,619.3
MPOVinf, mean ± SD	7,454.4 ± 2,692.6

GCC, ganglion cell complex; MPOV, macular pigment optical volume; NFL, nerve fiber layer; PhR, photoreceptor; SD, standard deviation; VF, visual field.

Table 2.

Relationships Between MPOV With 10° Eccentricity and Age, AL, and Gender

Variable	Coefficient	P
Age (y)	238.2	<0.001
AL (mm)	−752.3	0.020
Male gender	723.1	0.55

AL, axial length.

Boldface entries indicate P values < 0.05.

Table 3.

Relationships Between Mean MPOV in a Ring-Shaped Area Between 2.5° and 10° Eccentricity and GCC, NFL, PhR, AL, and Age

Variables	Coefficient	P
GCC (µm)	−23.8	0.18
NFL (µm)	4.2	0.81
PhR (µm)	29.8	0.40
AL (mm)	−820.2	0.10
Age (y)	210.1	<0.001

Boldface entries indicate P values < 0.05.

Table 4 shows the relationships between VF sensitivities (VF_sup/inf) and variables of retinal structure, AL, and age. Significant structure–function relationships were found between GCC_sup, NFL_sup, and VF_inf (P < 0.001, linear mixed model) and GCC_inf, NFL_inf, and VF_sup (P = 0.0024 and P = 0.036, respectively). In contrast, MPOV_sup had no significant association with VF_inf, and similarly MPOV_inf had no significant association with VF_sup. AL and age were not significantly associated with either VF_inf or VF_sup.

Table 4.

Associations Between Sensitivities of VF and Variables of Retinal Structure, AL, and Age

	Inferior VF/Superior Retina		Superior VF/Inferior Retina
Variable	Coefficient	P	Coefficient	P
GCC (µm)	0.20	<0.001	0.24	0.007
NFL (µm)	0.45	<0.001	0.21	0.036
PhR (µm)	0.14	0.29	0.20	0.35
MPOV in the ring-shaped area	−0.00073	0.75	−0.00025	0.42
AL (mm)	−0.51	0.18	0.78	0.17
Age (y)	0.089	0.13	0.12	0.13

Boldface entries indicate P values < 0.05.

Table 5 presents the associations between MPOV_sup/inf in the ring-shaped area and retinal layer thickness, AL, and age. MPOV_sup showed no significant association with GCC_sup, NFL_sup, PhR_sup, or age (P > 0.05, linear mixed model). However, MPOV_sup was significantly lower in eyes with a longer AL (P < 0.001). In the inferior retina, MPOV_inf was not significantly associated with GCC_inf and NFL_inf (P > 0.05). In contrast, MPOV_inf was significantly reduced in eyes with a thinner PhR_inf, longer AL, and older age (P < 0.05).

Table 5.

Associations Between the MPOV in the Ring-Shaped Area and Retinal Layer Thickness

	Superior Retina/MPOVsup		Inferior Retina/MPOVinf
Variable	Coefficient	P	Coefficient	P
GCC (µm)	−18.4	0.16	−20.7	0.15
NFL (µm)	−11.3	0.36	13.2	0.33
PhR (µm)	−32.5	0.22	132.5	<0.001
AL (mm)	−577.7	<0.001	−315.2	0.010
Age (y)	36.2	0.088	89.5	<0.001

Boldface entries indicate P values < 0.05.

As shown in Supplementary Table S1, MP levels within 2.5° were higher in older individuals, but no significant correlation was found with AL and sex. Supplementary Table S2 shows the relationships between VF_sup/inf and the values of GCC_inf/sup, NFL_inf/sup, PhR_inf/sup, MPOV_inf/sup2.5, AL, and age. MPOV_inf/sup2.5 was not significantly associated with VF_sup/inf.

Discussion

This study investigated the association between MPOV and VF in glaucoma, focusing on MPOV relationships with structure parameters such as GCC and NFL thickness. The findings suggest that MPOV is not significantly associated with VF in either the superior or inferior retina. MPOV was also not substantially linked with GCC or NFL in superior and inferior retinas. MPOV was considerably lower in eyes with long AL in both superior and inferior retinas.

The association between MPOD and glaucoma has remained controversial and contentious.^{19–22,24–29,38} Two studies that measured MPOD using HFP reported that eyes with glaucoma had lower MPOD levels compared to healthy eyes.^21,22 However, in our previous analysis of 328 healthy Japanese eyes and 25 eyes with glaucoma, glaucoma was not identified as a factor affecting MPOV, and the average MPOV across these 353 eyes was 20,121 ± 6293.³⁹ Furthermore, we reported in another study³² that an average MPOV was 19,156.1 ± 6700.6 in 96 healthy Japanese eyes. The average MPOV of the current 218 eyes with glaucoma was similar at 19,187.2 ± 6700.2, showing no apparent difference from those in healthy eyes in the previous studies. Because individual differences in the distribution patterns of MP³² affect the MPOD at a certain eccentricity, it has been suggested that using the total pigment volume as an indicator is more appropriate.⁴⁰ Therefore, in this study, we used MPOV as the indicator instead of MPOD. Based on these findings, we considered that there is no substantial difference in MPOV between individuals with glaucoma and healthy individuals. Although it is beyond the scope of the current study, we would like to conduct a more detailed comparison between glaucoma and healthy eyes using these datasets, including, for example, propensity score matching, in the future.

No previous study has looked into the influence of MPOD on visual function in the context of the structure–function relationship in glaucoma. Additionally, prior studies have used sparse VF test grids in the macular region,^{21,22,24–29} which are insufficient for assessing macular visual function in glaucoma.^41,42 To address this limitation, the present study utilized the HFA 10-2 test, which provides 26 test points in the superior and inferior VF regions, spaced at 2° intervals, and the relationship between VF sensitivity and MP was evaluated using MPOV corresponding to the regions assessed in the VF sensitivity test. Furthermore, when evaluating the structure–function relationship in glaucoma, it is essential to include patients across various disease stages. The present study encompassed glaucomatous eyes ranging from early to advanced stages (mean VF_sup and VF_inf were 20.7 dB and 25.7 dB, respectively) (Table 1). Indeed, VF sensitivity showed a significant association with GCC and NFL thickness in both the superior and inferior retinas (Table 4). However, no significant correlation was observed between VF sensitivity and MPOV in either region (Table 4).

The structure–function relationship in glaucoma is complex, with factors such as a floor effect below a VF threshold of 20 dB.^43,44 Additionally, VF measurements become increasingly unreliable below this threshold,^44,45 and significant axonal loss can precede detectable VF defects.¹⁸ Given these complexities, the present study examined the association between MPOD and glaucoma progression by assessing its correlation with GCC and NFL thickness. In contrast to analyzing the fundus by dividing it into superior and inferior regions, the comparison between MPOV within 2.5° and 10° and GCC, NFL, and sensitivity of VF showed no significant relationships.

In macular degeneration, MP mitigates oxidative damage in photoreceptor and retinal pigment epithelial cells by absorbing blue light and quenching oxygen radicals,^46–48 thereby protecting against photooxidative stress-related disorders.^46–48 In contrast, GCC thinning in glaucoma results from axonal loss at the optic disc due to the elevated intraocular pressure.⁴⁹ In addition, glaucoma predominantly affects peripheral regions, whereas MP accumulates mainly around macula. Thus, the antioxidant properties of MP may not directly influence glaucoma pathogenesis, which could explain the lack of association between MPOD and GCC/NFL thickness in this study. Moreover, MPOD usually accumulates near fovea, such as within 2.5°. Thus the effect of carotenoids intake is sensitively represented by MPOV_2.5. Hence, we analyzed the association between VF_sup/VF_inf and MPOV_2.5, which revealed no significant relation between the MPOV2.5 and VF sensitivity (see Supplementary Table S2 for details). Nevertheless, this result does not entirely rule out the potential effect of MP on glare sensitivity in glaucomatous eyes, as this study did not assess glare disability in detail (e.g., wavelength-specific analyses). It has been reported that much MP improves contrast sensitivity and glare disability by reducing light scatter in healthy eyes.^5,6 By contrast, a previous study suggested that the effect of MP on glare disability in glaucoma may be wavelength dependent.²⁶ Although investigating this further was beyond the scope of the current study, future research is warranted to explore the role of MP in glare sensitivity.

As noted earlier, the structure–function relationship in glaucoma is complex, with factors such as a floor effect below a VF threshold of 20 dB.^43,44 Additionally, VF measurements become increasingly unreliable below this threshold,^44,45 and significant axonal loss can precede detectable VF defects.¹⁸ Given these complexities, the present study examined the association between MPOD and glaucoma progression by assessing its correlation with GCC and NFL thickness. The results showed no significant relationship in either the superior or inferior hemiretina.

Also, in macular degeneration, MP mitigates oxidative damage in photoreceptor and retinal pigment epithelial cells by absorbing blue light and quenching oxygen radicals,^46–48 thereby protecting against photooxidative stress-related disorders.^46–48 In contrast, GCC thinning in glaucoma results from axonal loss at the optic disc due to the elevated intraocular pressure.⁴⁹ In addition, glaucoma predominantly affects peripheral regions, whereas MP accumulates mainly around macula. Nonetheless, we investigated the effect of MP on glaucoma mainly outside the macular region, because MP could also be a marker of long-time lutein intake and the mechanism may be as well by a pathway targeting inflammation like in AMD. However, no association was observed between MPOV and VF or GCC thickness in glaucoma, although a possibility of type II error cannot be completely excluded. Thus, the antioxidant properties of MP may not directly influence glaucoma pathogenesis, which could explain the lack of association between MPOD and GCC/NFL thickness in this study.

The present findings do not contradict previous research suggesting that oxidative stress contributes to glaucoma or that carotenoid-rich and polyphenol-rich diets and supplements may be beneficial in glaucoma management. Intraocular carotenoids are present not only in MP but also in other ocular tissues, including the lens, iris, ciliary body, choroid, and retinal pigment epithelium.⁵ These carotenoids may help mitigate oxidative stress in the trabecular meshwork. Although the current study found no significant association between MP and glaucoma, further research is needed to explore the potential effects of carotenoids in other ocular regions. Additionally, carotenoids are present in the brain, where they are thought to play a role in preventing neurodegeneration through their antioxidant properties.⁵⁰ Future studies should therefore investigate their potential neuroprotective effects on the optic nerve.

In the present study, MPOD was significantly reduced in eyes with longer AL in both superior and inferior retinas (Table 5). This finding is consistent with a previous study reporting an inverse relationship between MPOD and AL⁵¹ that was attributed to the known inverse relationship between MPOD and retinal thickness.^52–55 Notably, a significant inverse relationship was observed between MPOD_inf and PhR_inf but not between MPOD_sup and PhR_sup (Table 5). This discrepancy may be due to the greater susceptibility of the inferior retina to retinal deformation (i.e., PhR thinning) resulting from ocular elongation. For example, common myopic retinal changes, such as chorioretinal atrophy and myopic conus, are more frequently observed in the inferior retina. In contrast, no significant association was observed between VF_sup/VF_inf and MPOV_2.5 (Supplementary Table S2). This is because the retinal deformation due to the elongation of eyeball tends to be marginal in this area compared to the outer retinal region.

This study has strengths and several limitations. The strengths are as follows. Previous studies showing an inverse association between MPOD and GCC have had certain limitations. For example, one investigation focused only on patients with fovea-involved versus non-involved glaucoma²⁸ and included fewer than 100 participants.^27,28 Additionally, MPOD was measured using HFP²⁸ or single-wavelength reflectometry.²⁷ To the best of our knowledge, ours is the first study to examine the relationship between MPOD and GCC/NFL thickness using two-wavelength autofluorescence spectroscopy (SPECTRALIS OCT) in a sufficiently large glaucoma cohort.

The limitations are as follows. First, more reliable VF measurements in glaucoma could be obtained using microperimetry with eye-tracking features, such as the NIDEK MP-3.⁵⁶ Future studies should assess the effect of MPOD on VF using such advanced VF testing methods. Second, this study examined only the cross-sectional relationship between MPOD and glaucoma. A recent study suggested that MPOD may have a long-term protective effect against glaucoma progression.²⁴ Further research is needed to explore this potential role. Third, extracting MPOD data from clinical devices, such as the SPECTRALIS OCT, remains challenging in real-world clinical settings. Finally, the segmentation algorithms differ between the RS-3000 and SPECTRALIS OCT platforms, which may have influenced the absolute thickness values.

Conclusions

The present study suggests a null association between MPOV and VF as well as between MPOV and GCC/NFL thickness in glaucoma.