Examination of optical coherence tomography findings in patients with pregabalin use disorder

Subjects and clinical assessments

Between December 2023 and February 2024, 467 individuals applied to the probation clinic at İzmir Democracy University. In accordance with Turkey’s national policy, individuals involved in the use, purchase, or possession of controlled substances are mandated to attend the probation clinic. All participants were administered the SCID-5-CV (Structured Clinical Interview for DSM-5) (First et al., 2016) by the same psychiatrist. Comprehensive ophthalmologic examinations were conducted in the Department of Ophthalmology, including assessments of best corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopy, and fundus examination. The control group comprised hospital employees, including secretaries, cleaning staff, and security personnel, who had no history of substance use other than tobacco and no systemic medical conditions or medication usage.

Inclusion/exclusion criteria

Male participants aged between 18 and 45 were included in the study. Participants with comorbid psychiatric disorders, except for tobacco use disorder and personality disorders, were excluded. Exclusions also applied to individuals with neurological, immunological, or systemic diseases, as well as primary ophthalmological conditions such as glaucoma or retinal diseases. Additionally, participants with conditions that could affect image quality or measurement values, including high refractive errors and cataracts, were excluded. Only patients and controls with normal eye findings—defined as an intraocular pressure (IOP) lower than 21 mmHg, a refraction lower than 0.50 diopters both spherically and cylindrically, and no anterior or posterior segment pathologies as detected by slit-lamp biomicroscopy—were included in the study. Of the 467 individuals who applied to the probation clinic, 102 were diagnosed with Pregabalin Use Disorder (PGUD) following psychiatric evaluations and toxicological analyses. Of these, 12 were excluded due to being outside the age range of 18 to 45 years, and two females were excluded from the study. After excluding individuals with primary ophthalmological diseases, with conditions that could affect image quality or measurement values, those taking medications, and polysubstance users, the final analysis included 35 controls, and 34 participants diagnosed with Pregabalin Use Disorder (PGUD).

Spectral domain optical coherence tomography measurements

Spectral Domain Optical Coherence Tomography (SD-OCT) (DRI-OCT Triton, Topcon, Inc., Tokyo, Japan) measurements were performed to analyze RNFL, GCL-IPL, and GCC thickness. The images were evaluated blindly by two ophthalmologists in the Department of Ophthalmology. RNFL thickness values were recorded across four quadrants (superior, temporal, inferior, and nasal). GCL-IPL and GCC thickness values were measured in six sectors (superior, superotemporal, superonasal, inferior, inferotemporal, and inferonasal) (Figs. 1 and 2). The SD-OCT device’s automatic calculation and reporting system was used to analyze these values within each group. OCT measurements were taken for both eyes, but only the data from the left eye were used for statistical analysis.

Statistical methods

Statistical analyses were conducted using SPSS 25 (IBM Corporation, Armonk, New York, USA). Descriptive statistics were calculated as mean, frequency and percentage. Prior to comparisons, all data distributions were assessed using the Kolmogorov-Smirnov test. Categorical data were compared using the Pearson Chi-square test. Parametric tests (Independent t-test) were employed for normally distributed data, while non-parametric tests (Mann-Whitney U) were utilized for non-normally distributed data. Pearson correlation analysis was used to examine the relationships between the duration of Pregabalin use, age, and OCT parameters.

All retinal layers were compared between the control group and the Pregabalin group, and regression analyses were conducted to understand the effect of duration and smoking on the layers. Linear regression analyses were conducted to evaluate the potential effect of usage duration (in months) on different OCT measurements. A general linear model (GLM) was used to assess the impact of smoking and pregabalin use on all OCT measurements between the pregabalin and the control group. To evaluate the interactions between groups and the potential effects of smoking, group (PGUD/Control), smoking status, and the interaction between these two factors were included in the model. A p-value of < 0.05 was considered statistically significant for all tests.

Socio-demographic and clinical data

The study included thirty-four patients with PGUD and thirty-five controls. The mean age of the PGUD and control groups was 30.67 ± 7.59 and 30.71 ± 9.29, respectively. There was no significant difference between the groups in terms of age (p = 0.000). All participants in both groups were male. The proportion of smokers was higher in the PGUD group (p = 0.000). Thirty-two (94.1%) of the patients with PGUD and twelve (34.2%) of the controls were smokers. There was no significant difference between the groups in terms of marital status (p = 0.184). In the PGUD group, 14 participants (41.1%) completed primary education, 14 (41.1%) had secondary education, and six (17.6%) completed high school. In the control group, eight participants (22.8%) completed secondary education, eight (22.8%) completed high school, and 19 (54.2%) had undergraduate education. The difference in educational attainment between the groups was statistically significant (p < 0.001). In the PGUD group, 21 participants (61.8%) were employed, while 13 participants (38.2%) were unemployed. Additionally, 16 participants (47.1%) in the PGUD group had health insurance, whereas 18 participants (52.9%) did not. In the control group, all participants were hospital staff, meaning they were both employed and had health insurance (100%). Therefore, no comparisons were made between the groups regarding employment status and health insurance coverage (not applicable (N/A)). The mean duration of pregabalin use in the PGUD group was 62.26 ± 40.09 months (min: 12, max: 153), and the mean daily dosage was 1,129.41 ± 601.40 mg (min: 300, max: 3,600). The socio-demographic and clinical features of the groups are given in Table 1.

OCT findings

RNFL thickness was evaluated in four quadrants (inferior, superior, nasal, temporal). GCL-IPL and GCC thickness were evaluated in six sectors (superior, superonasal, inferonasal, inferior, inferotemporal, superotemporal). There was no significant difference between the groups in any sector or quadrant (p > 0.05 for all comparisons). OCT measurements are shown in Table 2. The impact of smoking and pregabalin use on all OCT measurements was assessed using General Linear Models (GLM). Overall, the models did not significantly explain the variance in any OCT measurements. For the RNFL measurements, none of the variables showed significant effects: RNFL-inferior (R² = 0.003, F = 0.024, p = 0.878), RNFL-superior (R² = 0.010, F = 0.001, p = 0.980), RNFL-nasal (R² = 0.133, F = 0.987, p = 0.324), and RNFL-temporal (R² = 0.047, F = 0.332, p = 0.566). Similarly, GCL-IPL measurements did not reveal any significant impact, including GCL-IPL superior (R² = 0.033, F = 0.133, p = 0.717), GCL-IPL superonasal (R² = 0.058, F = 0.026, p = 0.874), GCL-IPL inferonasal (R² = 0.034, F = 0.236, p = 0.629), GCL-IPL inferior (R² = 0.061, F = 0.901, p = 0.346), GCL-IPL inferotemporal (R² = 0.017, F = 0.097, p = 0.756), and GCL-IPL superotemporal (R² = 0.008, F = 0.046, p = 0.831). The GCC measurements were also unaffected, as indicated by GCC superior (R² = 0.004, F = 0.195, p = 0.661), GCC superonasal (R² = 0.021, F = 0.527, p = 0.470), GCC inferonasal (R² = 0.004, F = 0.117, p = 0.734), GCC inferior (R² = 0.011, F = 0.649, p = 0.424), GCC inferotemporal (R² = 0.029, F = 0.007, p = 0.933), and GCC superotemporal (R² = 0.007, F = 0.188, p = 0.666).

Correlations between pregabalin use and OCT parameters

RNFL superior (p = 0.011, r = −0.431), GCL-IPL superior (p = 0.011, r = −0.431), GCL-IPL superotemporal (p = 0.024, r = −0.386), GCL-IPL superonasal (p = 0.020, r = −0.300), and GCC inferonasal (p = 0.044, r = −0.348) measurements were negatively correlated with age. GCL-IPL inferior (p = 0.031, r = 0.370), GCL-IPL inferotemporal (p = 0.029, r = 0.376), GCC inferonasal (p = 0.040, r = 0.354), and GCC inferior (p = 0.018, r = 0.402) thickness were positively correlated with the duration of pregabalin use. Linear regression analyses were conducted to assess the impact of the duration of use (in months) on four retinal layers. The models for GCL-IPL inferior (R² = 0.139, F (1,32) = 5.148, p = 0.030), GCC inferior (R² = 0.147, F (1,32) = 5.521, p = 0.025), and GCL-IPL inferotemporal (R² = 0.140, F (1,32) = 5.219, p = 0.029) were statistically significant, explaining 13.9%, 14.7%, and 14.0% of the variance, respectively. However, the model for GCC inferonasal did not reach statistical significance (R² = 0.106, F (1,32) = 3.806, p = 0.060). The relationship between the duration of pregabalin use and the four retinal layers (GCL-IPL inferotemporal, GCL-IPL inferior, GCC inferonasal, and GCC inferior) is illustrated in Fig. 3. There was no other significant correlation between OCT measurements and dosage, age, or duration of use (p > 0.05). Dosage and all OCT measurements were negatively correlated, but none of them were at a significant level (p > 0.05). The correlations between age, duration, dosage, and OCT measurements are shown in Table 3.