Ocular symptoms caused by Sick House Syndrome (Sick House Syndrome and Ocular Symptoms)

Key points at a glance

Key points of this condition

• Sick building syndrome is a syndrome caused by exposure to volatile organic compounds (VOCs) released from new building materials and furniture, leading to mucous membrane irritation symptoms in the eyes, nose, throat, and other areas, as well as general symptoms.
• Eye symptoms commonly include eye strain, dry-eye-like dryness, conjunctival redness, light sensitivity, and eye pain. They are much more likely to appear as a visual problem related to higher brain function than as a problem of the eyeball itself.
• The main causative substances are formaldehyde (indoor guideline value 0.08 ppm), toluene, xylene, and paradichlorobenzene, and the provisional target value for total VOCs (TVOC) is 400 μg/m³²⁾.
• For diagnosis, the medical interview is most important, and it is necessary to confirm the temporal relationship between symptom onset and environmental changes after moving into a new building, renovation, or relocation. Improvement of symptoms after removing the cause is the key to diagnosis.
• Ophthalmic diagnostic criteria were proposed by Ishikawa et al. and are based on eye symptoms, environmental exposure history, and improvement after removal⁸⁾.
• The most important treatment is avoiding exposure to the causative substances (thorough ventilation and use of low-VOC building materials), and eye symptoms are treated with symptomatic care such as artificial tears.
• Some cases become chronic as multiple chemical sensitivity (MCS), and there is wide individual variation. Severe cases require coordination with environmental medicine and psychosomatic medicine.

1. What is sick house syndrome and what are its eye symptoms?

Sick house syndrome refers to a range of symptoms, including irritation of the eyes, nose, and throat, that appear after indoor exposure to volatile organic compounds (VOCs) released from new building materials, furniture, adhesives, and similar sources. When similar symptoms occur in poorly ventilated buildings such as offices or schools, it is called sick building syndrome. Both are included in the concept of multiple chemical sensitivity (MCS), in which even very small exposures to chemicals or substances from daily life can cause health problems, and there is large individual variation.

The eyes are mucosal organs that are easily affected by VOC irritation, and eye strain, conjunctival redness, and dry-eye-like symptoms often appear. In ophthalmology, it is notable that symptoms are far more often seen as higher brain function problems related to vision rather than as structural damage to the eyeball itself.

The main causative substances and the Ministry of Health, Labour and Welfare’s indoor concentration guideline values are shown below²⁾.

• Formaldehyde: Released from plywood and wallpaper adhesives. The strongest direct irritant to the eyes and nasal mucosa. Guideline value: 0.08 ppm (100 μg/m³)
• Toluene: Derived from paints and adhesives. Strong effect on the central nervous system. Guideline value: 0.07 ppm (260 μg/m³)
• Xylene: Derived from paints and solvents. Guideline value: 0.20 ppm (870 μg/m³)
• Paradichlorobenzene: Derived from mothballs and toilet deodorizers. Guideline value: 0.04 ppm (240 μg/m³)
• TVOC (total volatile organic compounds): provisional target value 400 μg/m³²⁾

In the 2003 revision of the Building Standards Act (measures against sick house syndrome), 24-hour ventilation systems became mandatory for essentially all buildings²⁾. A labeling system for building materials based on formaldehyde emissions (F☆☆☆☆ is the highest grade) was also introduced, and low-VOC materials have become more widely used.

Q Can sick house syndrome cause eye symptoms?

A

The eye is a mucosal organ easily exposed to direct irritation from VOCs, so eye symptoms occur frequently in sick house syndrome. The main symptoms are eye strain, redness, dryness (dry-eye-like symptoms), photophobia, and eye pain. It is also known that chemicals can affect the central nervous system and cause higher brain dysfunction related to vision (fluctuating vision, visual discomfort, and accommodative dysfunction). If symptoms began after moving into a new building, renovation, or relocation, sick house syndrome should be considered.

2. Characteristics of eye symptoms

Hasanreisoglu M, Avisar R. Thygeson’s superficial punctate keratitis: long-term topical cyclosporin A therapy. Cases Journal. 2008. Figure 1. Source ID: commons.wikimedia.org/wiki/File:Thygeson%27s_superficial_punctate_keratitis.jpg. License: CC BY 2.0.

In the anterior segment photograph, fine pale gray punctate subepithelial opacities are scattered across the cornea (Thygeson punctate superficial keratopathy). This corresponds to the corneal epithelial damage and dry-eye-like findings caused by VOC exposure described in the section Characteristics of eye symptoms.

The main characteristics of eye symptoms in sick house syndrome are as follows.

• Eye strain (asthenopia): The most common eye symptom. It arises from a combination of accommodative load and effects on the central nervous system³⁾
• Dry-eye-like symptoms: Abnormalities of the ocular surface caused by increased tear evaporation and goblet cell damage⁴⁾. They appear as dryness, foreign-body sensation, and eye discomfort
• Conjunctival redness and itching: Direct chemical irritation of the conjunctival mucosa by VOCs³⁾
• Photophobia (light sensitivity): Light hypersensitivity mediated by trigeminal nerve stimulation
• Eye pain: Pain caused by chemical irritation and neurogenic inflammation³⁾
• Visual higher-order brain dysfunction: fluctuating vision, visual discomfort, and accommodative problems. Symptoms often appear this way rather than from the eyeball itself

A dose-response relationship has been observed between formaldehyde exposure levels and the appearance of eye symptoms. When indoor levels exceed the guideline value (0.08 ppm), reports of eye symptoms increase significantly¹⁾.

VOC / indoor concentration	Eye and nasal mucosal irritation	Nervous system symptoms
Formaldehyde 0.08 ppm or higher	Increased eye and nasal irritation symptoms	Headache
Formaldehyde 0.5–1.0 ppm	Strong eye and nasal irritation	Fatigue and reduced concentration
Toluene 0.07 ppm or higher	Mild eye irritation	Predominantly central nervous system symptoms
TVOC 400 μg/m³ or higher	combined mucosal irritation	increase in nonspecific complaints

Eye symptoms of sick building syndrome can resemble allergic conjunctivitis, so it is important to differentiate them⁵⁾. Allergic conjunctivitis is mediated by antigen-specific IgE, whereas sick building syndrome is mainly caused by chemical irritation of the mucosa.

Q How are the eye symptoms of sick building syndrome different from allergies?

A

Allergic conjunctivitis involves antigen-specific IgE antibodies against antigens such as pollen and dust mites, and is an immune reaction in which itching, redness, and tearing occur each time there is antigen exposure. In contrast, eye symptoms of sick building syndrome are mainly caused by direct irritation of the mucosa by chemicals such as VOCs, and are independent of the immune mechanism (IgE). In the history, it is important to check the timing in relation to environmental changes such as a new home, remodeling, or moving, and to confirm whether symptoms improve with ventilation or after going outside. Even if blood tests (specific IgE antibodies) are negative, chemical sensitivity may still be possible.

3. Causative substances and disease mechanism

Main causative substances

The main causative substances in sick building syndrome and their sources are shown below¹⁾.

Substance name	Main source	Main effects on the eyes and nervous system	Guideline value
Formaldehyde	Plywood, MDF, wallpaper adhesive, insulation material	Direct irritation of the eyes and nasal mucosa (strongest)	0.08 ppm (100 μg/m³)2)
Toluene	Paints, adhesives, lacquer	Mainly central nervous system symptoms (headache, fatigue)	0.07 ppm (260 μg/m³)2)
Xylene	Paints, solvents, caulking compounds	Central nervous system and eye irritation	0.20 ppm (870 μg/m³)2)
Paradichlorobenzene	Moth repellent / toilet deodorizer	Eye and nasal mucosal irritation	0.04 ppm (240 μg/m³)2)
Styrene	Polystyrene insulation material	Eye irritation and fatigue	0.05 ppm (220 μg/m³)2)

VOC emissions increase as room temperature and humidity rise. In hot, humid summer conditions, especially high concentrations of VOCs are emitted soon after new construction or renovation⁶⁾.

Transition to Multiple Chemical Sensitivity (MCS)

Multiple Chemical Sensitivity (MCS) is a condition in which exposure to trace amounts of chemicals triggers symptoms across multiple organs and systems, and it is sometimes considered a chronic form of sick house syndrome⁷⁾. Involvement of central sensitization has been suggested, and once sensitized, reactions can occur even with extremely small exposures. Diagnostic criteria for MCS remain debated, and no objective biomarker has been established at present⁷⁾.

4. Diagnosis and testing methods

Ophthalmic diagnosis of Sick House Syndrome is mainly an exclusion diagnosis, and the key points are history taking and evaluation of environmental factors.

History taking (most important)

• Check whether symptoms are related in time to new construction, renovation, or moving.
• Symptoms appearing at work, school, etc. (possible sick building syndrome)
• Changes in symptoms with ventilation, going outside, or travel (if they improve with an environmental change, this strongly suggests it)
• Whether housemates or coworkers have similar symptoms
• Types of building materials, furniture, insect repellents, and air fresheners used

Ophthalmic diagnostic criteria

According to the ophthalmic diagnostic criteria proposed by Tetsu Ishikawa and colleagues, the requirements are: 1) the presence of eye symptoms, 2) confirmation of environmental exposure history (new construction, renovation, etc.), and 3) improvement of symptoms after removing the cause⁸⁾. A definitive diagnosis based on ophthalmology alone is difficult, and collaboration with indoor air environment measurements is essential.

Ophthalmic examination items

• Visual acuity and refraction tests: Evaluate underlying causes of the symptoms (such as refractive error)
• Tear tests: Confirm reduced Schirmer test results (tear secretion) and shortened BUT (tear film break-up time)
• Anterior segment slit-lamp microscopy: Presence or absence of conjunctival hyperemia, papillary hypertrophy, and corneal epithelial damage
• Accommodation function test: Evaluation of accommodative spasm and accommodative insufficiency. Estimation of higher brain dysfunction related to vision³⁾
• Allergy testing: Differentiation from allergic conjunctivitis by blood test (specific IgE antibodies)⁵⁾

Environmental assessment

• Indoor air quality measurement: direct measurement of formaldehyde and TVOC concentrations²⁾
• QOL questionnaire: quantitative assessment of systemic symptoms using the Indoor Air Quality Health Impact Survey⁹⁾

Q Can sick house syndrome be diagnosed by an ophthalmologist?

A

Definitive diagnosis based on ophthalmology alone is difficult. In eye care, the role is to quantitatively assess eye symptoms (tear tests, accommodation function tests, allergy tests, etc.) and rule out other conditions such as allergic conjunctivitis, dry eye, and VDT syndrome. A definitive diagnosis requires coordination with indoor air quality measurements (formaldehyde and TVOC concentrations), and multidisciplinary collaboration with architects, environmental medicine specialists, internal medicine, and psychosomatic medicine is recommended. If the history shows that symptoms started after moving into a new home, remodeling, or relocating, and improve after ventilation or going outside, that strongly supports the suspicion.

5. Standard treatment

Avoiding the cause (most important)

Avoiding exposure is the core of treatment for sick house syndrome.

• Thorough ventilation: Proper operation of 24-hour ventilation systems. Actively ventilate by opening windows²⁾
• Bake-out method: A method that promotes VOC release by repeating high heat and ventilation. Before moving in, ventilate for 3 to 7 days at 20 to 30°C to lower VOC levels⁶⁾
• Choose low-VOC building materials: Select materials rated F☆☆☆☆ (formaldehyde emission 0.005 mg/m²·h or less)²⁾
• Ventilation period after new construction or renovation: Make sure there is enough ventilation time before moving in (at least 1 to 3 months)
• Remove the source: Review the use of insect repellents and air fresheners

Checklist for improving the indoor environment

Please check the following items.

Ventilation equipment: Is the 24-hour ventilation system working properly? Are the filters cleaned regularly?

Building materials and furniture: Does newly brought-in furniture have a strong smell? Have you checked the F☆☆☆☆ label?

Review chemical products: Is the amount of insect repellents, air fresheners, and deodorants appropriate?

Ventilation habits: Do you open the windows wide for about 10 to 15 minutes once or twice a day?

Environmental measurement: If symptoms continue, consider asking about indoor air quality testing.

Symptomatic treatment for eye symptoms

• Artificial tear eye drops: Protect the ocular surface and replace moisture. Preservative-free products such as Soft Santear are preferable. Use 5–6 times a day
• Hyaluronic acid eye drops (Hyalein 0.1%): Effective when there is corneal epithelial damage. Use 5–6 times a day
• Choosing preservative-free eye drops: Patients with sick house syndrome may have heightened sensitivity to chemicals, so it is preferable to avoid added irritation from preservatives (such as benzalkonium chloride)
• Managing accommodative dysfunction: Improve the VDT work environment (screen position, distance, lighting) and provide appropriate refractive correction³⁾
• Cases with allergies: Use antiallergy eye drops (antihistamines and mediator-release inhibitors) as appropriate

Systemic management and multidisciplinary collaboration

• Severe cases or suspected MCS: Collaboration with an environmental medicine clinic, psychosomatic medicine, and internal medicine is needed⁷⁾
• Diagnosis and treatment of chemical sensitivity: Evaluation at a specialized facility is recommended
• Cases caused by the work environment: Consider collaboration with an occupational physician and an occupational health consultant

Q How can eye symptoms caused by sick house syndrome be improved?

A

The most important measure is to avoid exposure to the causative substance (VOC). Proper use of 24-hour ventilation systems, regular window ventilation, use of low-VOC building materials, and carrying out the bake-out method are the fundamental measures to lower indoor VOC levels below the guideline values. For eye symptoms, combine preservative-free artificial tears (5–6 times a day) with hyaluronic acid eye drops (Hyalein 0.1%) as symptomatic treatment. If symptoms do not improve or systemic symptoms are strong, consider referral to a specialist in environmental medicine.

6. Pathophysiology and detailed mechanism of onset

Ocular surface injury caused by VOCs

VOCs, including formaldehyde, directly damage the epithelial cells of the cornea and conjunctiva. When the mucosal barrier breaks down, the tear film becomes unstable and dry-eye-like symptoms appear⁴⁾. Goblet cells, which are essential for producing mucin in the tear film, are also damaged by VOC irritation, further reducing tear film stability⁴⁾.

Trigeminal nerve stimulation and neurogenic inflammation

Formaldehyde directly stimulates the trigeminal nerve endings of the cornea and conjunctiva (TRPA1 channel)¹⁾. Stimulation of the trigeminal nerve causes eye pain and light sensitivity. In addition, release of substance P and CGRP (calcitonin gene-related peptide) from nerve endings triggers neurogenic inflammation, leading to dilation of the conjunctival blood vessels (redness) and increased vascular permeability¹⁰⁾.

Oxidative stress and ocular surface injury

Metabolites of VOCs promote the production of reactive oxygen species (ROS). Oxidative stress damages the cell membranes of the ocular surface epithelium and increases the production of inflammatory cytokines¹⁰⁾. This process is similar to dry-eye pathology in dry environments, and VOC-related eye symptoms and dry eye may overlap.

Higher brain dysfunction affecting vision

The effects of chemicals on the central nervous system may appear more in the visual center (occipital and frontal lobes) than in the eyeball itself. They may present as fluctuating vision, visual discomfort, and accommodation problems, and it is a characteristic pattern of sick house syndrome and MCS to complain of strong eye symptoms despite few findings in the eye.

Central sensitization in multiple chemical sensitivity

In MCS, repeated low-dose exposure to VOCs is thought to cause central sensitization⁷⁾. After sensitization, even trace amounts of chemicals that do not affect healthy people can continue to trigger multi-organ, multisystem reactions. This mechanism can make sick house syndrome chronic and difficult to cure in some cases.

7. Latest research and future outlook

Notes on information still in the research stage

The following content includes topics that are in the research stage or under debate. It presents the current evidence neutrally and does not guarantee the effectiveness of any specific intervention.

Research on the correlation between indoor air quality and ocular surface parameters

Epidemiological studies evaluating correlations between indoor VOC concentrations and tear film BUT and corneal staining scores are accumulating⁴⁾. Improvements in ocular surface parameters with lower VOC concentrations have been reported, and quantifying the ophthalmic effects of improving indoor air quality remains a future challenge.

Large-scale epidemiological studies in workplace and school settings

Large-scale epidemiological studies are under way, mainly in Northern Europe, evaluating the relationship between the prevalence of sick building syndrome in office and school environments and indoor microbial, VOC, and TVOC concentrations⁹⁾. Its position as an occupational eye disease is being strengthened, and collaboration with occupational health management is advancing.

RCTs of low-VOC environmental interventions

RCTs evaluating the effects of interventions such as improved ventilation and switching to low-VOC building materials have been conducted⁶⁾, and significant correlations have been shown between the post-intervention decrease in formaldehyde concentrations and improvement in eye and nasal symptoms. Accumulation of large-scale, long-term follow-up data is expected in the future.

Assessment of new VOC sources

Electronic devices (3D printers, consumer laser printers, etc.) and e-cigarettes are drawing attention as new VOC sources. In particular, use in enclosed indoor spaces may be associated with increased eye symptoms, and evaluation studies are ongoing.

Objective diagnosis of multiple chemical sensitivity using biomarkers

There are no established biomarkers for MCS, making objective diagnosis difficult. Development is under way of objective diagnostic methods that combine oxidative stress markers, inflammatory cytokines, and neuro-sensitization markers⁷⁾. If put into practical use, they are expected to make objective assessment of sick house syndrome and evaluation of treatment effects possible.

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