Chemical injury of the ocular surface is a common and serious condition that can cause vision loss. Clinical findings show a wide spectrum from mild irritation to vision loss. Among the causes of chemical injury; materials used in household cleaning (detergent, disinfectant, etc.) as well as chemicals used in industry are also seen. The prognosis of eye injuries with chemicals is determined by the type, amount, and contact time of the substance.

Isocyanate is a raw material used in the production of all polyurethane materials and is used as a basic material in construction and industrial products. Three types of isocyanate toluene diisocyanate (TDI), polymethylene polyphenyl isocyanate (PAPI) and diphenylmethane diisocyanate (MDI) are used extensively. It has been stated that isocyanates in vapor form irritate mucosal structures, especially the conjunctiva and respiratory tract¹. Corneal edema due to TDI exposure has been reported previously². In the presentation of these cases; We aimed to discuss the mechanism of ocular surface injury after MDI exposure and its approach to this situation.

Three male patients, aged 19, 21 and 33 years old, presented to our clinic with the complaint of blurred vision. In the anamnesis of the patients, they worked in an insulation company and were admitted to the hospital after the increased blurred vision and stinging in the eyes. The working environments of the patients were closed areas and the items they used included MDI and PAPI.

In the physical examination of the 19-year-old patient; visual acuity (VA) was 0.5 bilaterally according to the Snellen chart, intraocular pressure (IOP) was 17 mmHg in the right eye and 16 mmHg in the left eye with applanation tonometry. Bilateral corneas were edematous, and occasionally stromal microcysts were observed (Figure 1).

Figure 1: Edematous cornea and occasionally stromal microcysts are observed.

Fundus could not be evaluated due to corneal edema. Central corneal tickness (CCT) was 513 µm in the right eye, 526 µm in the left eye (with Compact Touch STS/UBM Ultrasound Biomicroscope from Quantel Medical), and tear break-up time (TBUT) was 13 seconds for the right eye and 12 seconds for the left eye.

In the examination of 21 years old patient; VA was 0.7 in the right eye, 0.6 in the left eye according to the Snellen chart and 16 mmHg with bilateral applanation tonometry. Bilateral corneas were edematous but it was observed that corneal edema was less than first case (Figure 2).

Figure 2: Epithelial edema on the dome of the cornea.

Fundus examination was normal. CCT was measured as 530 µm in the right eye, 523 µm in the left eye, and bilateral TBUT was 15 seconds.

For the third patient, who was 33 years old, VA was 0.4 in the right eye and 0.5 in the left eye according to the Snellen chart. IOP was measured as 16 mmHg in the right eye and 18 mmHg in the left eye by applanation tonometry. Bilateral corneas were edematous (Figure 3).

Figure 3: Minimal corneal epithelial edema of the right eye.

CCT was measured as 535 µm in the right eye, 547 µm in the left eye, and TBUT was 12 seconds for the right eye and 13 seconds for the left eye.

After obtaining the consent of the patients, they were admitted to Fırat University Department of Ophthalmolgy clinic. To all the three patients; topical steroid (0.1% dexamethasone) was applied 5 times a day, artificial tear (polyvinyl alcohol) was applied 8 times a day and gel (carbomer) was applied bilaterally 5 times a day. On the second day of the treatment, 5% hypertonic ophthalmic solution was applied 5 times per day to the first and third patients due to severe corneal edema. On the 4th day of the treatment, it was observed that the corneal edema of the patients reduced and their visual acuity improved bilaterally. The patients were discharged by recommending outpatient clinic control with same treatment. All the three patients had full visual acuity, their corneas were completely transparent, and there were no stained area on the ocular surface when they were observed in the outpatient clinic controls one month later. CCT was measured as 487 µm in the right eye, 503 µm in the left eye; 512 µm, 508 µm; and 517 µm, 525 µm; respectively.

Written informed consent was obtained from the patients for publication of this case report and accompanying images.

MDI can cause serious respiratory diseases such as occupational asthma, hypersensitivity pneumonia or alveolitis, and skin irritation. It is important to use a suitable mask when working with MDI and similar substances that evaporate and can cause toxic effects on sensitive tissues³. Also, it should be kept in mind that it may affect sensitive tissues such as conjunctiva and cornea. This risk may increase especially for those who work in indoor environments where air circulation is low. In our cases, presenting three patients with similar complaints at the same time suggests that it may be a toxic substance, but if only one patient was affected we might not noticed.

The cornea is a transparent tissue and its continuation depends on the functional of the epithelial and endothelial layers of the cornea ⁴. Transparency loss due to corneal edema; although it mostly develops as a result of endothelial dysfunction, it may rarely occur due to epithelial and tear film layer disorders. It has been stated that epithelial and endothelial cells provide the balance of corneal hydration by using active energy and the tear film layer contributes to corneal transparency by serving as an oxygen source for the anterior cell layers of the cornea⁵. Mishima et al.⁶ showed that the tear film layer creates hypertonic osmotic pressure to expel excess dissolved water from the epithelium. Therefore, any defect in energy metabolism in both the endothelial layer and the epithelial layer of the cornea may cause deterioration in corneal hydration and loss of corneal transparency.

The mechanism of corneal edema formation caused by diisocyanates is not fully known yet. It has been reported in corneal edema caused by endothelial cell dysfunction, fluid leaks into the stroma, as a result, stromal thickness increases to approximately 30%, and then epithelial edema occurs⁷. Davies et al.⁸ showed that diisocyanate impairs endothelial energy metabolism by inhibiting 3', 5'-cyclic-adenosine-monophosphate formation. Since disruptions in corneal epithelial energy metabolism also cause corneal edema, this mechanism should not be ignored in treatment planning. In this case series, we observed there was approximately a 15% difference (less than 30% difference stated in the literature) between pre-treatment corneal thickness and post-treatment corneal turbidity completely disappeared. These data support a deterioration in the epithelial layer rather than a deterioration in the corneal endothelium. We think that people who are engaged in insulation work may develop pathologies related to prospective corneal toxicity, so long-term follow-up of these patients will be useful.

In conclusion, the toxic effect of isocyanates on corneal epithelial metabolism may be the cause of corneal epithelial edema. It should be kept in mind that workers who use protective equipment such as masks and gloves can apply only with eye complaints. In acute bilateral corneal edema, toxic gas exposure should be kept in mind.