JSM Arthritis

Quantification of Progressive Retinal Thinning In Patients with Fibromyalgia Syndrome over a Period of 5 Years

Research Article | Open Access | Volume 4 | Issue 1

  • 1. Ophthalmology Department, Miguel Servet University Hospital, Spain
  • 2. Miguel Servet Ophthalmology Research and Innovative Group (GIMSO), Aragon Institute for Health Research (IIS Aragón), University of Zaragoza, Spain
  • 3. Psychiatry Department, Red de Investigación en Atención primaria (REDIAPP), Miguel Servet University Hospital, Zaragoza, Spain
  • 4. University of Zaragoza (Unizar), Zaragoza, Spain
+ Show More - Show Less
Corresponding Authors
Maria Satue, C/ Padre Arrupe, Consultas Externas de Oftalmología 50009 -Zaragoza, Spain, Tel: 0034.976.76.55.58

Purpose: To quantify changes in visual function parameters and the macular neuroretina of patients with Fibromyalgia (FM) over 5 years, compared with controls.

Methods: Eighty patients with FM and 38 healthy subjects were included in a prospective observational study and underwent visual acuity (VA) evaluation with ETDRS chart, contrast sensitivity vision (CSV) with CSV 1000E test, and retinal evaluation using Spectralis Optical coherence tomography (OCT). All subjects were re-evaluated after 5 years to quantify changes in visual function parameters and ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness. The relationship between progressive structural, functional and disease severity changes was analysed. Additionally, patients were classified into three different groups to analyse progression depending on the disease phenotype.

Results: When compared with controls, patients with FM presented worse low contrast VA (p=0.024), and low frequency CSV (p=0.004) after a 5-year follow up. A progressive decrease affecting the GCL thickness (nasal 1, p=0.004; temporal 1, p<0.001; inferior 1, p=0.001) and the RNFL (nasal 1 and 2, p<0.001; superior 1, p<0.001; and inferior 1, p=0.002) was observed in patients over the monitoring time. Changes affecting the GCL were correlated with progression in disease severity scores (EQ-5D, r=0.560, p<0.001; FIQ, r=-0.470, p=0.003). Correlations between structural changes and disease severity scores were only observed in the atypical and biologic phenotypes.

Conclusions: Progressive visual dysfunction and retinal neurodegeneration was detected in FM patients. The evaluation of visual parameters and GCL/ RNFL thickness using SD-OCT can be useful to monitor FM progression.


•    Fibromyalgia
•    Contrast sensitivity vision
•    Ganglion cell layer
•    Retinal nerve fiber layer
•    Optical coherence tomography
•    Neurodegeneration


Satue M, Vicente MJ, Perez-Velilla J, Tello A, Vilades E, et al. (2021) Quantification of Progressive Retinal Thinning In Patients with Fibromyalgia Syndrome over a Period of 5 Years. JSM Arthritis 4(1): 1031.


Fibromyalgia (FM) presents widespread pain and generalized hyperalgesia for mechanical pressure (1). It affects approximately a 2% the world population and it is also called chronic pain syndrome or chronic fatigue syndrome (1,2). These patients’ quality of life experiences from mild to severe affectation (1-3).

Some theories nowadays suggest that the clinical presentation of FM is determined by central phenomena instead of peripheral dysfunction; nevertheless, the pathophysiology is not entirely comprehended. It has been suggested an implication of a possible imbalance of inflammatory biomarkers (4). Furthermore, patients with FM syndrome have been reported to experience changes in brain perfusion, structure and functional responses to pain (5-7).

In recent years, Multiple sclerosis, Parkinson disease or Alzheimer are examples of neurodegenerative processes in which the retinal ganglion cell layer (GCL) has been recognized as a useful biomarker for diagnosis and monitoring of such diseases (8-11). Moreover, other mental disorders (such as schizophrenia and bipolar syndrome) also presented retinal neurodegeneration, providing new information of the pathophysiology of psychiatric diseases (12-14). Observable/visible retinal changes were recently appreciated/found to be present in FM by optical coherence tomography (OCT) (15), increasing the number of neurologic syndromes with a possible neurodegenerative course underneath what is known to its pathophysiology nowadays.

Supervising retinal and visual changes over time in individuals with neurodegenerative processes is of a great relevance: it contributes to a further understanding of the annual neurodegeneration rate, provide clinicians with a biomarker of progression and even of prognosis, and permits to evaluate the effectivity of different treatments (16,17). Progressive visual dysfunction and neuroretinal degeneration in patients with FM were evaluated over a period of 5 years in the present study. Very little literature on ophthalmological changes in FM syndrome has been written, and to date, this is the first longitudinal study with the objective of assessing progressive changes in these patients.


Some of the procedures described in this document were detailed elsewhere (15,17). Confirmed FM patients were incorporated into this prospective longitudinal study with a follow-up of 5 years. A power calculation was performed, based in the results of our previous studies and assuming an alpha error of 5% and a beta error of 10%. A standard sample size equation was used to calculate the number of subjects required, that was 37 in each group (FM patients and healthy controls). To further increase the power of the study, we included more FM patients. Finally, 80 suitable individuals were included in the study and sex and age-matched with 38 healthy controls. Both groups were evaluated at baseline (recruitment and data collection: 2015) and at 5 years (re-evaluation and data collection/analysis: 2020). All procedures adhered to the tenets of the Declaration of Helsinki and all participants provided written informed consent to participate in the study.

Patients were selected from the Primary Care Research Group Study population of FM patients in Zaragoza, Spain. This research group provided all patients that were included in the first cohort in 2015 and results of the cross-sectional study have been published elsewhere (15). FM diagnosis was based on the 1990 American College of Rheumatology criteria for FM (18). A specializing FM psychiatrist, who evaluated the patients and was blind to the ophthalmology assessment recorded type of FM, disease duration, age at diagnosis and treatment. Severity of FM was established using the Fibromyalgia Impact Questionnaire (FIQ); and evaluation of activities of daily living and impact on quality of life using the Euro Quality of Life 5D (EQ-5D) scale. The ophthalmologic evaluation consisted of anterior segment assessment, best-corrected visual acuity based on the Snellen scale, visual field test, OCT evaluation, and a funduscopic exam. All individuals were evaluated by two neuro-ophthalmologists who were blind to the psychiatrist evaluation. The exclusion criteria consisted of: patients with BCVA lower than 0.4 (decimal, measured with Snellen chart), significant refractive errors (>5 diopters of spherical equivalent refraction or 3 diopters of astigmatism), intraocular pressure ≥21 mmHg, media opacifications, concomitant ocular diseases (including history of glaucoma or retinal pathology) and systemic conditions (especially neurodegenerative processes) that could affect the visual system. No history and no evidence of ocular or neurologic disease of any nature had been previously observed in healthy controls; their best-corrected visual acuity (BCVA) was >0.4. Each eye was considered independently and only one eye of each subject was randomly included unless only one of the eyes met the exclusion criteria.

Visual Function Evaluation

Visual function was tested by assessing photopic BCVA and contrast sensitivity vision (CSV). BCVA was evaluated using an ETDRS chart at two different contrast levels: 100% (High contrast VA [HCVA], using ETDRS chart) and 2.50%, (Low contrast VA [LCVA], using Low-Contrast ETDRS chart). We obtained all measurements under monocular vision and controlled lighting conditions with best correction. Results were recorded in LogMar. CSV, which offers more precise data about the visual pathway than BCVA, was evaluated using the CSV 1000E test. This test evaluates contrast sensitivity at 4 different spatial frequencies (3, 6, 12, and 18 cycles per degree [cpd]). The chart comprises four rows with 17 circular patches each. The patches present a grating that decreases in contrast moving from left to right across the row. The subject has to indicate whether the grating appears in the top patch or the bottom patch for each column. Each contrast value for each spatial frequency was transformed into a logarithmic scale according to standardized values. All patients were evaluated at a distance of 2.5 meters from the chart under monocular vision

Macular Structural Evaluation

Structural measurements of the retina were obtained using the Spectralis OCT device (Heidelberg Engineering, Germany). Retinal segmentation was performed using the fast macular protocol for Spectralis OCT to identify the RNFL and the GCL and to quantify its thickness. Signal strength is indicated by a blue quality bar in the image (range is 0-40, where 0 is categorized as poor quality and 40 as excellent). We included images with a score higher than 25 in the analyses. Adhering to the suggested procedure, the subject’s pupil was first centered and focused on an iris viewing camera, and then the device’s image calibrating system was used to optimize the retina visualization. Once the saturation and placement of the scan was optimal, we always activated the Automatic Real-time Tracking (ART) and maintained the image quality using the smaller live image screen at the bottom of the monitor. The device obtained perifoveal retinal scans comprising 25 single horizontal axial scans in a scanning area of 666 square mm. Registered parameters included the 9 ETDRS macular areas, which are displayed as superior 1, nasal 1, inferior 1 and temporal 1, corresponding to the inner ring; and superior 2, nasal 2, inferior 2 and temporal 2, corresponding to the outer ring. Additionally, average central thickness and foveal (center) thickness were recorded.

Fibromyalgia Evaluation

A specialized psychiatrist evaluated all the patients and classified them following FM subgrouping at the Miguel Servet Hospital Fibromyalgia Unit, based on the pressure-pain thresholds and psychologic factors described by Giesecke et al (19). The Giesecke classification includes three subgroups of FM: Subgroup1 (atypical): low tenderness, moderate depression/ anxiety, moderate catastrophizing, and moderate control over pain; Subgroup 2 (depressive): high tenderness, high depression/ anxiety, high catastrophizing, and low control over pain; and Subgroup 3 (biologic): high tenderness, low depression/anxiety, low catastrophizing, and high control over pain.

Additionally, each subject with FM also completed the FIQ and the EQ-5D questionnaire, to check the impact of the disease and the quality of life and activities of daily living respectively. The approved Spanish form of these questionnaires was used (20,21). For the FIQ, patients were assigned a score from 0 to 100. The higher the score, the greater the disease impact. The EQ-5D comprises five questions with three response categories concerning the following dimensions: mobility, self-care, usual activities, pain, and anxiety/depression. The EQ-5D results are expressed as a percentage from 0 to 100, being 100 the best health status possible, and 0 the worst status possible in these patients (22).

Statistical Analysis

All subjects were evaluated after 5 years from baseline (2020 and 2015, respectively), and the 5-year change per subject on each variable was calculated. Modifier variables were age, sex, and intraocular pressure. Statistical analysis was performed using commercial predictive analytics software (SPSS, version 20.0; SPSS, Inc., Chicago, IL). The normality of the sample distribution was assessed using the Kolmogorov-Smirnov test. Since most variables did not follow normal distribution non-parametric tests were performed for calculations. FM disease scores, and visual function and GCL thickness parameters were compared between baseline and the 5-year visit using the Wilcoxon test for paired data. Changes registered during the follow-up were calculated for each subject in every variable and were compared between FM patients and healthy controls using Mann Whitney’s U test. A p value of <0.05 was considered statistically significant; however, Bonferroni correction for multiple comparisons was applied to avoid bias (see tables).

An additional analysis in FM phenotypes was performed: changes observed in the different FM phenotypes were compared between subgroups using the ANOVA and Post hoc analysis, to analyze whether any subgroup presented greater change in time compared to the other subgroups.

Possible associations between structural and functional changes and FM parameters (type of FM, impact of disease and EQ-5D score) were analyzed by means of Spearman’s correlation Test.


Eighty eyes of 80 patients and 38 eyes of 38 healthy individuals were included in this longitudinal study. Age, sex, and intraocular pressure did not differ significantly between the groups, nor at baseline or at 5-year follow up. Mean disease duration at 5 years was 12.84±3.95 years. The FM phenotype distribution was: biologic FM, 18 patients (22.50%); depressive FM, 22 patients (27.5%); atypical FM, 40 patients (50%). The FIQ mean score at baseline was 61.05±19.57 and 64.85±19.39 at 5-year follow up (p=0.458). The EQ-5D mean score was 44.38±18.63 at baseline, and 39.78±16.48 at 5-year follow up (p=0.03). (All demographic variables and significance are included in (Table 1).

After 5 years, patients with FM presented significantly worse visual function outcomes compared to baseline affecting CSV in all 4 spatial frequencies (Table 2). BCVA (at 100% and 2.50% contrast) did not change significantly over time. Healthy controls did not present significant changes over time (Table 2) in any of the visual function variables.

When we compared the 5-year change between patients and controls, patients presented greater change (worse) in low contrast BCVA (p=0.024) and CSV affecting low frequencies (3 cpd, p=0.004; 6 cpd, p=0.004) compared to controls (Table 2).

A significant reduction of the macular GCL was observed in patients after 5 years, affecting the nasal (N1, p=0.004), temporal (T1, p<0.001) and inferior (I1, p=0.001) quadrants (Table 3). Additionally, there was a significant reduction of the RNFL in the nasal (N1, p<0.001; N2, p<0.001), superior (S1, p<0.001; S2, p<0.001) and inferior (I1, p=0.002) quadrants. Healthy controls did not present any significant changes in macular measurements over time (table 3). No significant differences were observed between patients and controls when the 5-year change in structural measurements was compared.

Changes Based on Fibromyalgia Phenotype

All patients were divided into three different groups based on their FM phenotype (subgroup 1: atypical; subgroup 2: depressive; subgroup 3: biologic) and differences in the 5-year change between groups were calculated using ANOVA test and post hoc analysis. Statistical differences between the different phenotypes were only observed in the CSV results, affecting the spatial frequency of 12 cpd (high frequency) (ANOVA p=0.019). Post hoc analysis revealed that the atypical phenotype (subgroup 1) presented worse CSV at 12 cpd over time compared to the depressive phenotype (p=0.019) but this reduction was not significant when compared to the biologic phenotype (p=0.139). Change over time in disease severity parameters and structural variables was not significantly different between the FM phenotypes (These data are not shown in tables, data concerning the ANOVA-Post hoc analysis will be provided upon request to the corresponding author).


The correlation between the 5-year change in the FM scores and functional /structural parameters was calculated using the Spearman Rho test. A strong inverse correlation between the 5-year change in the EQ-5D score and the FIQ results (r=-0.700, p<0.001) was observed.

A moderate correlation was observed between progressive thinning in the central average thickness of the GCL and progression of disease severity as measured with the EQ-5D score (r=0.560, p=0.001) and the FIQ (r= -0.470, p=0.003). Additionally, progressive thinning of the RNFL was associated with worsening of LCVA (these results can be observed in table 4).

When correlations were calculated based on FM phenotypes, the atypical phenotype (subgroup 1) presented important correlations between a higher number of variables than any of the other subgroups. Change in the EQ-5D score was associated with changes in the FIQ (r= -0.64, p=0.006), and similar to what was observed in the total FM group, progressive thinning of the GCL (average central) was significantly correlated with the EQ-5D score (r=0.675, p= 0.032) and the FIQ score (r=-0.665, p=0.032).

Changes in the average central thickness of the GCL were also strongly correlated with worsening of the EQ-5D score in the biologic phenotype (r=0.708, p= 0.001).

Changes in the EQ-5D score over the 5-year period were strongly correlated with changes in the FIQ results in all three FM phenotypes; however, the depressive phenotype presented the strongest correlation (r=-0.84, p=<0.001).

Significant correlations found in the different FM phenotypes can be seen in table 5. Non-significant data do not appear in the tables.

Table 1: Demographic data of patients and controls included in the study, at baseline and at 5-year follow up. Bold numbers indicate statistical significance.

 Variable  FM  Controls  p
baseline 51.98±8.08 49.50±9.75 0.151
5 year 56.51±8.13 59.35±6.92 0.223
Sex M/F %      
baseline 4.9/95.1 16.7/83.3 0.255
5 year 5.1/94.9 13.9/77.8 0.330
baseline 13.22±2.33 13.95±3.56 0.399
5 year 13.88±3.08 14.02±2.97 0.219
Age at diagnosis 43.44±8.35    
Disease phenotype      
Atypical   18    
Depressive   22    
Biologic   40    
baseline 7.80±4.60    
5 year 12.84±3.95    
Eq5d score      
baseline 44.38±18.63   0.030
5 year 39.78±16.48  
FIQ score      
baseline 61.05±19.57   0.458
5 year 64.85±19.39  

Table 2: Visual function parameters in patients with fibromyalgia and healthy controls, at baseline and 5-year follow up. P* indicates comparison between data from baseline and 5 years in each group, using Wilcoxon test (paired data). Change was calculated for each variable in each patient. P indicates comparison between changes observed in patients and controls, calculated by Mann whitney’s U test. Bold numbers indicate significance according to Bonferroni’s test for multiple comparisons. Significance value based on Bonferroni correction for multiple comparisons: VA EDTRS, 0.025; CSV1000E, 0.0125.

Variable FM baseline FM 5 year Change P* Healthy baseline Healthy 5 years change P* P
VA 100 0.04±0.18 0.01±0.17 -0.03±0.22 0.448 0.05±0.07 -0.06±0.11 -0.17±0.11 0.039 0.029
VA 2.50 0.30±0.13 0.34±0.19 0.03±0.18 0.258 0.39±0.10 0.35±0.14 -0.18±0.08 0.109 0.024
CSV 3 cpd 1.74±0.15 1.58±0.15 -0.18±0.16 <0.001 1.64±0.12 5.15±1.28 3.35±0.95 0.109 0.004
CSV 6 cpd 1.91±0.17 1.79±0.14 -0.11±0.18 0.002 1.71±0.19 5.00±1.87 2.95±2.00 0.109 0.004
CSV 12 cpd 1.53±0.25 1.29±0.27 -0.23±0.25 <0.001 1.410.14± 4.00±2.12 1.25±1.98 0.285 0.089
CSV 18 cpd 1.02±0.26 0.85±0.17 -0.15±0.28 0.009 1.16±0.24 4.15±2.23 1.83±2.24 0.285 0.175

Table 3: Retinal structural parameters in patients with fibromyalgia and healthy controls, at baseline and 5-year follow up. P* indicates comparison between data from baseline and 5 years in each group, using Wilcoxon test (paired data). Change was calculated for each variable in each patient. P indicates comparison between changes observed in patients and controls, calculated by Mann whitney’s U test. Bold numbers indicate significance according to Bonferroni’s test for multiple comparisons. Abbreviations: Min, minimum; FM, fibromyalgia; GCL, ganglion cell layer; IPL, inner plexiform layer.

Variable FM baseline FM 5 year Change  P* Healthy baseline Healthy 5 years change  P*  P
Average central 16.22±4.22 16.40±5.14 0.13±3.12 0.591 15.58±2.85 16.40±4.28 0.57±4.14 0.750 0.993
Nasal 1 51.24±5.79 48.48±6.96 -1.52±3.34 0.004 50.42±3.93 50.23±5.28 -0.57±3.06 0.185 0.272
Nasal 2 37.41±4.00 36.83±4.39 0.28±1.97 0.446 36.95±3.59 38.13±4.53 0.89±1.88 0.057 0.335
Superior 1  50.78±5.85 49.64±5.47 -0.39±2.03 0.116 51.53±4.81 51.83±5.69 -0.26±2.74 0.320 0.925
Superior 2 35.54±4.10 34.03±4.27 -0.28±1.33 0.162 34.53±3.27 35.97±3.81 1.15±2.16 0.037 0.007
Temporal 1 45.93±4.82 44.01±5.68 -1.86±3.28 <0.001 45.58±4.65 46.00±5.56 -0.10±3.12 0.913 0.073
Temporal 2  34.48±4.28 33.76±4.89 -0.21±2.50 0.255 34.89±4.42 35.83±4.28 0.63±2.47 0.289 0.158
Inferior 1 51.57±5.11 49.10±6.70 -1.47±3.94 0.001 51.32±4.36 51.37±5.34 -0.94±1.54 0.020 0.743
Inferior 2 31.72±3.51 30.58±3.98 -0.78±1.94 0.006 32.42±3.59 32.57±4.08 0.36±1.97 0.464 0.025
Center 4.88±3.48 6.11±3.59 1.27±3.14 0.022 3.42±2.26 5.37±4.10 1.94±4.36 0.040 0.869
Average central 12.92±2.13 12.38±2.26 -0.32±1.57 0.175 13.20±1.87 12.79±3.38 0.20±4.49 0.496 0.521
Nasal 1 22.12±2.21 21.57±6.80 -1.85±2.28 <0.001 20.40±1.95 20.13±3.61 -0.70±4.29 0.147 0.556
Nasal 2 52.60±9.35 48.82±11.19 -2.97±4.11 <0.001 47.30±14.44 44.33±13.03 -3.80±13.58 0.192 0.893
Superior 1 23.80±2.84 23.05±3.73 -1.20±1.97 <0.001 24.50±3.10 24.46±5.52 0.80±7.16 0.766 0.41
Superior 2 37.96±6.13 36.77±6.46 -1.35±3.43 0.010 38.40±6.46 38.13±5.54 -1.00±5.03 0.497 0.951
Temporal 1 18.12±1.27 18.34±3.54 -0.62±1.68 0.030 18.40±2.45 18.38±3.53 -0.30±1.25 0.417  0.584
Temporal 2  19.52±1.98 19.87±4.04 -0.52±1.46 0.020 21.80±9.07 23.79±11.20 3.40±9.52 0.340 0.067
Inferior 1 27.24±3.66 25.90±4.50 -1.60±2.87 0.002 23.60±3.62 24.96±4.01 -0.40±1.95 0.495 0.220
Inferior 2 42.84±10.12 41.57±11.61 -0.50±4.58 0.381 40.70±9.65 38.04±6.82 -2.80±4.70 0.084 0.119
Center 1.95±3.49 3.58±4.93 1.72±4.80 0.017 2.88±3.64 4.06±4.29 2.00±5.50 0.461 0.778

To our knowledge, this is the first longitudinal study assessing progressive changes in the functional and retinal parameters of patients suffering from FM. At the end of 5 years, our patients presented progressive CSV loss and progressive retinal thinning affecting the macular area. GCL thickness was found to be remarkably reduced in our patients after 5 years, particularly affecting the nasal, temporal and inferior quadrants. The RNFL was also reduced in our patients; moreover, we ound significant thinning slightly affecting more areas than the GCL, suggesting that the progressive change observed in the neuroretina of these patients might not be local (i.e. not primarily affecting the ganglion cells) but retrograde damage from neurodegeneration occurring in the central nervous system. The retina (specially the neuroretina, composed by the GCL complex and their axons) is a window to the central nervous system, axonal loss secondary to neurodegenerative processes such as multiple sclerosis or Parkinson disease has been priory detected by OCT measurements of the inner retinal layers (8, 9, 24). Nevertheless, whether damage can be observed earlier in the GCL or the RNFL is still controversial depending on the disease and published series. Most studies on multiple sclerosis point to the GCL as the most sensitive biomarker for neurodegeneration (25,26). Our current results suggest that neurodegeneration is present in FM patients and causes progressive thinning on the GCL and the RNFL of the macular area. More studies are needed to corroborate our findings and to elucidate whether the RNFL might be a more sensitive biomarker than the GCL for monitoring disease progression in these patients.

Scarce literature on retinal degeneration in FM patients is available. We could not find any published research into axonal loss in FM other than our earlier cross-sectional results, which showed RNFL loss in the peripapillary area and a tendency towards GCL loss in the macular zone (15). Investigation on retinal perfusion in FM patients is also almost inexistent (27,28). Bambo et al evaluated perfusion at the optic nerve head of FM patients using colorimetric analysis software and observed that hemoglobin levels were reduced in patients with FM, particularly within the neuro-retinal rim. Nevertheless, the macular area was not evaluated. (28) contributed to new insights to the pathophysiology of this syndrome by detecting choroidal thinning in the macular area of FM patients. This decline in blood perfusion was suggested to be related to changes in autonomic nervous system functioning. 

Nowadays, views of the etiology of FM indicate an involvement of central phenomena with the central nervous system playing a leading role (29). Some abnormalities in sensory signaling which have also been proved to be related to central sensitization in these patients include changes in key neurotransmitters and reduction of descending control (30). Moreover, there are possible altered pain pathways present as abnormal amplifications of pain in FM patients (31,32) and a chronic pro-inflammatory state (both in the CNS and in peripheral tissues). Nonetheless, theories explaining retinal thinning in FM syndrome are scarce. Earlier investigations described neurobiologic and brain structure irregularities in these patients (1,7). Clauw et al reported a central sensitization in FM provoked by neurobiologic abnormalities. Our previous findings support this theory and suggest that neurodegeneration is causing RNFL depletion and contributing to the pathology of FM. The theory of neurodegeneration causing RFNL depletion and contributing to the pathology of FM is suggested and supported by our previous discoveries.

However, basing on Bambo et al and Ulusoy et al research, progressive retinal thinning could also be caused by alterations in ocular perfusion in these subjects. Earlier studies on FM syndrome found hypoperfusion (both central and peripheric) as the most important factor in the origin of chronic abnormal pain in these subjects (33-35). As the choroid irrigates only the external retinal layers, more studies on retinal blood flow are still needed in these patients to analyze whether a decrease in the irrigation of the retinal internal layers (neuroretina) exists and to determine a possible correlation between GCL thinning and retinal vascularization changes.

An important finding in our study is the significant correlation observed between disease severity progression, as measured with the EQ-5D scale and the FIQ, and progressive thinning of the GCL (central average thickness). Currently, there are no specific nor definitive diagnostic tests for FM syndrome. Our results provide a new option not only to facilitate the diagnosis of FM but also to monitor disease progression. The ability to evaluate the retinal ganglion cells as an indicator of disease progression is an important advance, and this examination can be easily implemented in clinical practice, because OCT tests are noninvasive, fast, and comfortable for patients, as well as inexpensive.

Another important finding in our study concerns results observed by disease phenotype. There were no differences in the 5-year change of the EQ-5D score between the three FM phenotypes (meaning, no phenotype worsened more than the others during the 5-year period) and no differences concerning GCL loss. However, the atypical phenotype presented worse CSV (affecting a specific spatial frequency) than the depressive phenotype. Despite no differences could be found between the other groups affecting this functional parameter, it might help orientate diagnosis when other diagnostic tests are insufficient to stablish a definite diagnosis on a specific phenotype.

Additionally, both the atypical and the biologic phenotypes presented a strong correlation between disease severity scores and progressive thinning affecting the average central thickness of the GCL. This association was not found in the depressive phenotype, suggesting that neurodegeneration might have a minor role in patients with depressive FM. Interestingly, previous OCT studies suggested neurodegeneration is not present in patients with major depression syndrome (36), whereas neurodegeneration has been observed in the retina of patients suffering other diseases associated with depression, such as bipolar disorder (14,37). Our results on FM subtypes have not been priory reported, we believe this study might give clinicians new clues to better understand the pathophysiology of the different FM phenotypes.

No specific and conclusive tests on which to establish FM diagnosis, possible treatment alternatives or to comprehend the pathophysiology of this process exist nowadays. Thus, the search for key biomarkers is essential in these patients. Autotaxin, brain derived neurotrophic factor and other pro-inflammatory factors (such as TNF-α, IL-6, IL-10) have been found in the cerebrospinal fluid and plasma and/or serum of FM patients (38-40) and in addition there are published studies which use these markers to monitor different therapies (4). Our results might provide new options not only to facilitate the diagnosis of FM, but also to monitor these patients by using GCL results and visual function parameters as a possible biomarker for disease evolution, to follow the different disease subtypes, and be of additional support for new pathophysiology research.

This study has some limitations. First, as the sample was too small in our opinion, no logistic regression analysis in phenotypes groups was performed. Maybe due to the sample size too, our previous cross-sectional study discovered that ophthalmologic parameters did not predict disease severity in FM patients. Nevertheless, in the present study, a significant correlation between disease severity scores and alterations in GCL thickness was observed, implying that OCT changes might serve as a potential biomarker for disease progression, although prognosis is not feasible through this imaging device yet.

Second, despite changes were observed after a 5-year time lapse in the retina of FM patients as calculated by paired data analysis, no significant differences were observed between quantitative change in patients and controls over the same period. We believe this might be due the small size of the control sample, and that significant differences between both groups might be detectable if the number of controls could be increased. Last, apart from our own study, we could not find any previous published studies on retinal or visual function changes and FM syndrome, so the results of this study cannot be supported by earlier findings of external investigators. The reason is uncertain for us, although one might be the lack of positive results. This would be highly counter-productive for this type of research, as all results require to be supported (or contradict) by new findings, not only for our group, also for science in general.

In conclusion, FM causes progressive visual function loss and retinal neurodegeneration observable by SD-OCT. Progressive retinal thinning is related to an increase in disease severity, and this relationship is even stronger in the atypical and biologic FM phenotypes. This is the first longitudinal study on progressive visual and structural changes in FM syndrome. We think more studies with a larger sample size would be essential, particularly in the evaluation of treatment efficacy and the study of the pathophysiology of the disease.

Table 4: Significant associations found between structural parameters and functional parameters in patients with FM syndrome.

Structural parameter Functional parameter   R   P
CL avg central EQ5D 0.560 <0.001
FIQ -0.470 0.003
RNFL Nasal 1 VA ETDRS 2.50 -0.408 0.009
RNFL Nasal 2 VA ETDRS 2.50 -0.560 <0.001
RNFL Inferior 1 VA ETDRS 2.50 -0.400 0.011

Table 5: Significant associations found in the different fibromyalgia phenotypes.

FM phenotype Variables associated   R   P
Atypical EQ5D - FIQ -0.64 0.006
EQ5D –GCL avg central 0.675 0.032
FIQ - GCL avg central -0.665 0.036
RNFL nasal 2 – ETDRS 2.50 -0.740  0.036
Depressive Eq5D - FIQ -0.84 <0.001
Biologic Eq5D - FIQ -0.80 <0.001
EQ5D-GCL avg central 0.708 0.001
RNFL inferior 2- ETDRS 2.50 -0.513 0.021



This research received no specific funding by any agency in the commercial or not-for-profit sectors. MS was supported by a competitive research contract from the Instituto de Salud Carlos III, Spain (Juan Rodes program: CM17/00010) and by PI17/01726 (Instituto de Salud Carlos III, Spain)


1. Clauw DJ. Fibromyalgia: a clinical review. JAMA. 2014;311:1547–1555.

2. Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG. Mood and anxiety disorders in chronic fatigue síndrome, fibromyalgia, and irritable bowel syndrome: results from the LifeLines cohort study. Psychosomatic Medicine.2015;77: 449–457.

3. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, et al. The American College of Rheumatology Preliminary Diagnostic Criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res. 2010;62: 600–610.

4. Montero-Marin J, Andrés-Rodríguez L, Tops M, Luciano JV, Navarro-Gil M, et al. Effects of attachment-based compassion therapy (ABCT) on brain-derived neurotrophic factor and low-grade inflammation among fibromyalgia patients: A randomized controlled trial. Sci Rep. 2019;9(1):15639.

5. Mountz JM, Bradley LA, Alarcon GS. Abnormal functional activity of the central nervous system in fibromialgia syndrome. Am J Med Sci. 1998; 315(6):385–396.

6. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum. 2002; 46(5):1333–1343.

7. Jensen KB, Srinivasan P, Spaeth R, Tan Y, Kosek E, Petzke F, et al. Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis Rheum. 2013; 65(12):3293–3303.

8. Garcia-Martin E, Rodriguez-Mena D, Herrero R, Almarcegui C, Dolz I, Martin J, et al. Neuro-ophthalmologic evaluation, quality of life and functional disability in MS patients. Neurology. 2013; 81(1):1–8.

9. Ratchford JN, Quigg ME, Conger A, Frohman T, Frohman E, et al. Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies. Neurology. 2009; 73(4):302–308.

10. Satue M, Seral M, Otin S, Alarcia R, Herrero R, Bambo MP, et al. Retinal thinning and correlation with functional disability in Parkinson’s disease patients. British Journal of Ophthalmology 2014;98(3):350- 355

11. Polo V, Garcia-Martin E, Pinilla J, Larrosa JM, Satue M, et al. Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer’s disease. Eye (Lond). 2014; 28(6):680–690.

12. Demmin DL, Mote J, Beaudette DM, Thompson JL, Silverstein SM. Retinal functioning and reward processing in schizophrenia. Schizophr Res. 2019; 219:25-33.

13. García-Portilla MP, García-Álvarez L, de la Fuente-Tomás L, VelascoIglesias Á, Sáiz PA, et al. Could structural changes in the retinal layers be a new biomarker of mental disorders? A systematic review and thematic synthesis. Rev Psiquiatr Salud Ment. 2019;12(2):116-129.

14. Garcia-Martin E, Gavin A, Garcia-Campayo J, Vilades E, Orduna E, et al. Visual function and retinal changes in patients with bipolar disorder. Retina. 2019;39(10):2012-2021.

15. Garcia-Martin E, Garcia-Campayo J, Puebla-Guedea M, Ascaso FJ, Roca M, et al. Fibromyalgia is correlated with retinal nerve fiber layer thinning. Plos One 2016;11(9): e0161574.

16. Garcia-Martin E, Ara JR, Martin J, Almarcegui C, Dolz I, et al. Retinal and optic nerve degeneration in patients with multiple sclerosis followed up for 5 years. Ophthalmology. 2017;124(5):688-696.

17. Satue M, Rodrigo MJ, Obis J, Vilades E, Gracia H, et al. Evaluation of progressive visual dysfunction and retinal degeneration in patients with Parkinson disease. Invest Ophthalmol Vis Sci. 2017;58(2):1151- 1157.

18. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee. Arthritis Rheum. 1990; 33(2):160–172.

19. Giesecke T, Williams DA, Harris RE, Cupps TR, Tian X, et al. Subgrouping of fibromialgia patients on the basis of pressure-pain thresholds and psychological factors. Arthritis Rheum. 2003; 48 (10):2916–2922.

20. Rivera J, Gonzalez T. The Fibromyalgia Impact Questionnaire: a validated Spanish version to assess the health status in women with fibromyalgia. Clin Exp Rheumatol. 2004; 22:554–560.

21. Badía X, Roset M, Herdman M, Segura A. La versión española del EuroQol: descripción y aplicaciones. Med Clin (Barc). 1999; 112:79– 86.

22. Kind P, Dolan P, Gudex C, Williams A. Variations in population health status: results from a United Kingdom national questionnaire survey. BMJ. 1998; 316(7133):736–741.

23. Felgueiras H, Parra J, Cruz S, Pereira P, Santos AF, et al. Dyschromatopsia in Multiple Sclerosis Patients: A Marker of Subclinical Involvement? J Neuroophthalmol. 2016;36(3):275-279.

24. Satue M, Obis J, Alarcia R, Orduna E, Rodrigo MJ, et al. Retinal and choroidal changes in patients with Parkinson’s disease detected by Swept source Optical coherence tomography. Current Eye Research 2018;43(1):109-115.

25. Petzold A, Balcer LJ, Calabresi PA, Costello F, Frohman TC, et al. Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 2017;16(10):797-812.

26. Lampert EJ, Andorra M, Torres-Torres R, Ortiz-Pérez S, Llufriu S, et al. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. J Neurol. 2015 Nov;262(11):2491-2497.

27. Bambo M, Garcia-Martin E, Gutierrez-Ruiz F, Magallon R, Roca M, et al. Study of perfusion changes in the optic disc of patients with fibromyalgia syndrome using new colorimetric analysis software. J Fr Ophtalmol. 2015 Sep;38(7):580-587.

28. Ulusoy MO, Kal A, I?ik-Ulusoy S Kal Ö. Choroidal thickness in patients with fibromyalgia and correlation with disease severity. . Indian J Ophthalmol. 2018;66(3):428-432.

29. Sawaddiruk, P., Paiboonworachat, S., Chattipakorn, N. & Chattipakorn, S. C. Alterations of brain activity in fibromyalgia patients. J Clin Neurosci. 2017;38: 13–22.

30. Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DL, et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016;157(8):1599–1606

31. Häuser, W. Ablin J, Fitzcharles MA, Littlejohn G, Luciano JV, Usui C, et al. Fibromyalgia. Nature Reviews Disease Primers 1, 15022 (2015).

32. Sluka, K. A. & Clauw, D. J. Neurobiology of fibromyalgia and chronic widespread pain. Neuroscience. 2016;338: 114–129.

33. Kulshreshtha P, Deepak KK. Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review. Cite this article Clin Physiol Funct Imaging. 2013;33(2):83-91.

34. Usui C, Hatta K, Doi N, Nakanishi A, Nakamura H, Nishioka K, et al. Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin. Arthritis Res Ther. 2010;12(2):R64.

35. Katz DL1, Greene L, Ali A, Faridi Z. The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation. Med Hypotheses. 2007;69(3):517-525.

36. Sönmez ?, Kö?ger F, Aykan Ü. Retinal nerve fiber layer thickness measurement by Spectral-domain optical coherence tomography in patients with major depressive disorder. Noro Psikiyatr Ars. 2017; 54(1):62-66.

37. Kalenderoglu A, Sevgi-Karadag A, Celik M, Egilmez OB, Han-Almis B, Ozen ME. Can the retinal ganglion cell layer (GCL) volume be a new marker to detect neurodegeneration in bipolar disorder? Compr Psychiatry. 2016; 67:66-72.

38. Rodriguez-Pintó, I., Agmon-Levin, N., Howard, A. & Shoenfeld, Y. Fibromyalgia and cytokines. Immunol Lett. 2014; 161: 200–203.

39. Üçeyler, N., Hauser, W. & Sommer, C. Systematic review with meta-analysis: cytokines in fibromyalgia syndrome. BMC Musculoskelet Disord. 2011;12: 245.

40. Lind AL, Just D, Mikus M, Fredolini C, Ioannou M, et al. CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia. J Pain Res. 2019;12:2875-2889.

Satue M, Vicente MJ, Perez-Velilla J, Tello A, Vilades E, et al. (2021) Quantification of Progressive Retinal Thinning In Patients with Fibromyalgia Syndrome over a Period of 5 Years. JSM Arthritis 4(1): 1031.

Received : 21 Sep 2021
Accepted : 05 Oct 2021
Published : 11 Oct 2021
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X