Chronic GVHD (cGVHD) is a predominant cause of mortality and disability not related to relapse; it occurs in 30 to 70% of patients. The majority of patients with cGVHD present with ocular involvement with a reported incidence of 40-60%. Symptoms can range from mild dry eye syndrome to severe epithelial defects that can generate corneal perforation and loss of vision. The most accepted pharmacological modality is the topical application of cyclosporine A; on the other hand, tacrolimus has shown greater immunosuppressive power when used in ocular GVHD. However, this effectiveness is limited since by the time the manifestations appear, there is already permanent damage to the lacrimal gland due to the lymphocytic infiltration; so it is necessary to use a prevention strategy before these manifestations appear. Previously, the employment of ocular cyclosporine drops as ocular GVHD prophylaxis was assessed to evaluate safety and effectiveness, showing that it is well tolerated and can limit the appearance of severe dry eye manifestations in a small group of patients. The purpose of this work is to compare the two modalities currently accepted for the treatment of the disease, but in a prophylactic way; topical ciclosporin A against topical tacrolimus, to determine the safety and efficiency of each of them as a preventive measure to limit the risk of developing the appearance of ocular cGVHD and the permanent consequences that this generates.

After being informed about the study and potential risks, all patients giving written informed consent will be assigned a participant number to anonymize their data and collect information, including age, sex, diagnosis, stage of disease, type of procedure, and conditioning chemotherapy. Additionally, an ophthalmology evaluation will be conducted in the Ophthalmology Department of the University Hospital of the U.A.N.L. by the study team of ophthalmologists, following a standardized method and using a worksheet for dry eye and ocular surface evaluation.

Participants will be randomized to receive either treatment arm A (cyclosporine eye drops) or treatment arm B (tacrolimus ointment) through a stratified method. After the hematopoietic stem cell transplant (HSCT), information will be collected, such as the transplant details (e.g., number of cluster of differentiation 34 [CD34] cells infused, cell source, and any complications during the procedure) and medications used for the systemic GVHD prophylaxis, as well as the graft date. In addition to the standard systemic management protocol for GVHD prevention of the transplant program of the Hematology Service of the Hospital University U.A.N.L. cyclosporine or tacrolimus will be administered to participants once grafting is demonstrated, defined as the presence in the blood count of a neutrophil count that is equal to or greater than to 500/mm3 and platelet count equal to or greater than 20,000/mm3.

• Treatment arm A: topical cyclosporine 0.1% ocular drops, twice daily, one drop in each eye, with a 12-hour difference between each dose, for 12 continuous months. The commercial presentation that we will use has the following formula: Each milliliter of 0.1% solution contains Cyclosporine A 10 mg, c.b.p 1.0 ml.
• Treatment arm B: tacrolimus ointment, to be applied approximately 1cm or the amount to cover the lower fornix twice a day in each eye, with a difference of 12 hours between each dose, for 12 continuous months. The presentation of the medicine in ointment has a 10 gr tube with 0.03% drug.

Ophthalmological evaluations will be carried out at the initial visit (before the bone marrow transplant) and scheduled subsequent visits: at the time of transplant graft (variable depending on the type of transplant, between days +10 and +21 approximately), and 3, 6, 9, and 12 months from the start of treatment (day of graft). Also, they will be evaluated during all follow-up visits to the transplant department of the Hematology Service, assessing adherence and tolerance to the medication through direct questioning. The severity of ocular GVHD will be established based on the NIH criteria and the severity criteria of the international consensus on the severity of chronic ocular GVHD (ICCGVHD)

Ophthalmological variables to be evaluated

• Tear breakup time, Schirmer's test, esthesiometry, Keratograph 5M Topographer Dry Eye Assessment, upper and lower tarsus Meibomian Gland imaging (Keratograph 5M), tear osmolarity, metalloproteinase 9 levels in tears.
• Corneal and conjunctival staining measured with the Oxford Scale and the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Scale and SICCA Ocular Staining Score (OSS).

Inclusion Criteria:

1. Patients undergoing allogeneic HSCT.
2. Patients 18 years of age or older.
3. Patients who agree to participate in the study and sign the informed consent document.

Exclusion Criteria:

1. Patients undergoing HSCT who do not continue their evaluation and follow-up in the Hematology Service of the University Hospital.
2. Patients under 18 years of age.
3. Patients who do not agree to participate in the study.
4. Patients diagnosed with previous rheumatic disease.
5. Patients with dermatological conditions undergoing systemic treatment.
6. Patients with uncontrolled thyroid disease.