Letter to the Editor: Clarifying the scope of integrated psycho-ophthalmology: Reply to commentary on ‘When eye disease affects the mind’

Abstract

The author of this letter critically examines Nagamine’s judgement of our pilot case series published in the World Journal of Clinical Cases relative to cohort characterization, study design, and findings interpretation. The group had a mixed neurologic picture, but in general consisted mostly of patients referred for complex psycho ophthalmologic evaluation because of autoimmune or demyelinating neurologic comorbidities, which reflect real-life tertiary practice. As it is designed as a feasibility study, the study was not designed as a clinical efficacy trial, but as a descriptive case series and not as an intervention trial, and that the conclusion is belies as an intervention trial. The link between eye disease burden and mental distress is not one-way but a two-way and multi-faceted one. The “vision-identity-autonomy” conceptual framework refers to a model that can propel the development of multisectoral initiatives for health and wellbeing, as well as equity-oriented research. We recognize the necessity for a more rigorous prospective study but feel that the clinical practicality of integrated care models for detection and management of psychological distress in complex ophthalmic populations merits consideration. The stimulation of dialogue enhances nomenclature, methodology and future suggested research. In this letter, we specifically mention that the clarification points are as per the original pilot case series, but the more general conceptual points are not per se supported by the pilot series, and must be seen as ‘exploratory’ and ‘hypothesis-generating’.

Key Words: Autoimmune diseases; Mental health; Ophthalmology; Psychological distress; Psycho-ophthalmology

Core Tip: The intention of the commentary is to delineate the ambit and meaning of the earlier published psyche-ophthalmology case series. The initial case series was an exploratory project of minor availability, feasibility and useful application from the clinical therapeutic point of view of a promising active holistic approach. The study looked at reciprocal relationship between eye disease and psychological distress, use of screening tools like Hospital Anxiety and Depression Scale and the exploratory nature of “vision-identity-autonomy” triad. This case series calls for additional controlled studies.

TO THE EDITOR

We appreciate Nagamine’s considerate comments in the World Journal of Clinical Cases as well as the chance to elaborate on the take-home message, aims and correct interpretation of our recent pilot case series[1]. We will particularly tackle the foremost methodological problems highlighted in the commentary: Diagnostic heterogeneity, design that is oriented to feasibility, lack of causal inference, exploratory nature of the “vision-identity-autonomy” framework, and correct interpretation of psychological screening instruments. For each finding, we will clarify whether the original finding is reconfirmed, narrowed, or reinterpreted as exploratory[2].

Cohort composition and diagnostic heterogeneity

We agree that diagnostic heterogeneity should be addressed explicitly. Our integrated clinic was established in a real-world tertiary care setting and, as such, reflects the profile of patients most referred for combined ophthalmologic and psychological assessment: Adults with complex inflammatory, autoimmune, degenerative, or otherwise rare and potentially sight-threatening eye disease. Although diagnostically diverse, the cohort shared several important clinical characteristics. In the series, 17 of 18 patients had an underlying systemic autoimmune, rheumatologic or demyelinating comorbidity while one patient had inherited retinal degeneration which was the main underlying ocular condition. Therefore, the motive for examining this heterogeneous group was more clinical than strictly nosological. In spite of different diagnoses, these patients shared a small number of overlapping features which had motivated referral; specifically, the burden of chronic illness, diagnostic uncertainty, symptom burden, treatment complexity, fear of visual loss, and disturbance of daily, social and work functioning[2]. Of late, we must concede that the paper title may have created the impression of a more homogeneous autoimmune population than the one that was actually studied. The future work may encapsulate the clinical realities around the autoimmunity eye diseases more effectively with more liberal descriptors such as complex psycho-ophthalmology referrals. Thus, the original findings should be interpreted as applying to a selected tertiary-care psycho-ophthalmology referral population, not to a uniform autoimmune ophthalmology cohort. Their generalizability to other ophthalmic populations, such as primary glaucoma or diabetic retinopathy in the absence of systemic autoimmune, rheumatologic, or demyelinating disease, remains limited and should be tested separately.

Study design and methodological limits

We agree that our report should be read as a feasibility-oriented, practice-based pilot study rather than as evidence of efficacy. By design, it was a descriptive consecutive case series conducted in routine clinical care, with the limitations inherent to a small, single-center, referral-based, uncontrolled, cross-sectional study using screening rather than diagnostic psychiatric tools[1,2]. The main contribution was therefore practical and descriptive: To show that brief mental health screening combined with a focused clinical interview can be incorporated into routine ophthalmic care and may help identify unmet psychological needs[1]. These design features also mean that the study cannot estimate prevalence, establish temporal or causal relationships, assess the effectiveness of the integrated care pathway, or support generalization to unselected ophthalmic populations. Therefore, the original result is best interpreted as evidence of clinical feasibility and unmet need, not as evidence of efficacy or population-level burden.

Association rather than causation

We agree that causal language requires caution. We recognize this as another key concern of the editorial and have therefore avoided interpreting the observed associations as evidence of directionality or mechanism. Our title was intended as a clinical framing device, not as a claim of one-way causality. The present data supports an association between ophthalmic disease burden, impaired functioning, and psychological distress in a selected referred population, but they do not show that eye disease alone causes psychiatric morbidity. The relationship is more likely bidirectional and influenced by multiple factors, including pre-existing vulnerability, systemic disease burden, pain, uncertainty, treatment load, and social context[1,2]. To differentiate among these three pathways, longitudinal assessments are required and not a snapshot one. Such as the temporal relationship of the eye and psychological symptoms, the correspondence of declared disability and ophthalmological signs and the patterns of treatment compliance and coping, and change after ophthalmic or psychological intervention may all be revealing. The best approach to assessment is by ophthalmic and mental health professionals, aware that any psychological influence on symptom awareness or adherence does not exclude co-existing ocular disease. The statement on temporal dynamics notes the importance of longitudinal studies with appropriate comparators[1]. As a result, the noted association is relevant clinically and does not turn the original study into a causal or mechanistic claim.

Exploratory conceptual framework

We appreciate the commentary’s request for a clearer definition of the “vision-identity-autonomy” axis. In our article, we used this formulation to organize themes that repeatedly emerged during semi-structured interviews, such as fear of blindness, altered self-image, loss of independence, work disruption, and uncertainty about the future[1,2]. Along with the ophthalmic evaluation, the semi-structured psychological assessments and questionnaires were administered by psychologists from the Psychology Unit of San Marco University Hospital. The themes stemmed from recurrent clinical problems that emerged during psychological examinations, not from the outcome of formal qualitative analysis. No prior qualitative methodology or independent thematic coding was applied as those procedures were beyond the scope of feasibility of the original pilot study.

Notably, this formulation is not positioned as a validated conclusion from the pilot dataset; rather, it is intended as a clinically grounded heuristic to organize recurrent themes in the interviews. We do agree, however, that this construct remained exploratory and was not formally operationalized in the pilot study. Future studies should operationalize these dimensions prior to evaluating the relationships between these and visual function, disease activity, treatment burden, and PROs[2]. This clarification restricts the way the framework can be interpreted as being related to a hypothesis-generating matter rather than a measure arising from the pilot study.

Screening rather than diagnosis

Screening is not diagnosis and we agree with that. In our clinical pathway, the Hospital Anxiety and Depression Scale was used solely as a brief screening tool, never as a stand-alone diagnostic tool[2]. This supports its initial use in nonpsychiatric medical settings and subsequent evidence for the usefulness of identifying possible anxiety and depression symptoms[3-6]. Nonetheless, its performance may change depending on population, clinical setting and cutoff used. Therefore, the scores from the questionnaire were interpreted alongside the semi-structured psychological interview and the clinical context. Hence, the higher Hospital Anxiety and Depression Scale ratings in the original series should not be interpreted as a psychiatric diagnosis but as a possible indication of psychological morbidity needing further investigation.

Ocular surface observations

We acknowledge that there should be a more explicit recognition of a confounding potential for ocular surface symptoms and psychological distress. Patients with an auto-immune or systemic inflammatory disease may experience ocular discomfort, pain, fatigue, sleep disturbance, treatment burden, and emotional distress either together, or in any combination thereof, and these may affect the perception of these symptoms and reported functional impairment[1,2]. Greater psychological distress may relate to a more severe performance in protective ocular symptoms. Further, persistent ocular discomfort may also contribute to anxiety, low mood and poor quality of life. Our pilot case series was of a descriptive and cross-sectional design and this did not permit us to unravel these overlapping pathways or establish the independent contribution of ocular surface disease and psychological factors.

Consequently, the ocular surface findings should not be interpreted as evidence of a direct or mechanistic relationship. Future studies should utilize validated questionnaires to assess ocular surface symptoms in conjunction with objective clinical measurement while also considering pain, systemic disease activity, treatment exposure, sleep disturbance and psychological factors. It would be important to perform longitudinal and multivariable analyses to determine whether psychological distress independently influences symptom perception or ocular surface disease independently contributes to the subsequent psychological burden.

Conclusion

A potential next step would be a multicenter longitudinal cohort which assesses patients at baseline, 6 months and 12 months with Hospital Anxiety and Depression Scale screening, SF12, semi-structured psychological assessment, objective visual function measures, and relevant clinico-demographic measures including ocular disease activity, pain burden, treatment exposure and functional status. An a priori sample size calculation for the primary outcome is needed, based on the anticipated change and variability, while taking into account anticipated dropout and using standard assumptions for statistical power and type I error. The estimates from the current pilot experience and the first longitudinal cohort can be used in this calculation.

The main result may be the longitudinal impact of psychological distress (Hospital Anxiety and Depression Scale) change; secondary outcome may be change in SF-12 mental and physical components, vision-related quality of life, patient-reported symptomatic burden, treatment adherence, appointment attendance, and use of psychological/psychiatric services. Comparator groups may consist of patients with chronic non-autoimmune ocular disorders matched for age, sex, and degree of visual impairment.

A further multicenter randomized controlled trial could compare usual ophthalmic care vs usual care plus an integrated psycho-ophthalmology package of standardized screening, brief psychoeducation, and facilitated access to psychological support. Participants were allocated to either group in a 1:1 ratio, with stratification by centre, baseline psychological distress and visual impairment severity. If randomization is not possible, a prospective matched comparison, using propensity-score methods, could be performed, but with greater risk of residual confounding.