The selection of patients was carried out in healthy individuals, over 18 years of age, with iris heterochromia (congenital-7% or acquired, secondary to topical medication-1%, trauma-0.5% or surgery-0.25%), nevus-0.25% and cosmetic cases-91%.
The exclusion criteria were: under 18 years old, personal or family history of glaucoma, chronic ocular pathology (uveitis, iritis, retinopathy, trauma), systemic inflammatory, infectious, or oncological diseases, chronic vascular diseases (diabetes, Raynaud), autoimmune diseases (rheumatoid arthritis, Crohn’s disease, ulcerous colitis, Behçet disease, lupus erythematosus, multiple sclerosis), serious psychological disorders or psychiatric diseases (depression, bipolar disorder, obsessive, compulsive, or paranoid patients or, in particular, those with body dysmorphia disorder). Specific cases of medical allergies or intolerances were also rejected, as well as the chronic consumption of anabolic, steroids, hormones, or drugs.
Regarding degrees of pigmentation, prior to 2019 only cases in grades I–III of the Eyecos ocular pigmentation classification (Fig. 2) were admitted, but in the final months and at present we began to accept grade IV cases, with very satisfactory results.
The indications to apply PCI have been alterations in iris pigmentation, which have included unilateral or bilateral, partial or complete, congenital heterochromia, single or multiple nevus, and acquired causes, secondary to trauma, surgical complications (cataracts), and due to iatrogenesis from the abuse of prostaglandin eye drops to lengthen eyelashes. The differential diagnosis between nevus and iris melanoma was performed using three methods: 1—color assessed with the IRÎZ Scanner (clear in nevus and almost black in melanomas); 2—thickness and stromal infiltration measured by OCT (nevus are superficial and do not infiltrate the stroma; but melanomas are very thick and deeply infiltrate the stromal layer); and 3—if still in doubt, an iris angiography can be performed (in nevus the pattern is like normal tissue; but in melanomas, a large nutrient vessel with strong extra vascular diffusion of fluorescein is easily seen). In relation to the patients who used prostaglandin drops, all of them were young and healthy. None of them had previous glaucoma, but the reason was only cosmetic for the lengthening of the eyelashes (Latisse®). Therefore, the choice of these candidates did not alter the validation of their results.
The most frequent reasons for interested patients were purely aesthetic (close to 91% of the total), without the presence of heterochromia. It surprised us that the stated reasons were not capricious, but rather a professional need (contract requirements for image professionals like models or actors), sentimental (specific preferences of their partner) and psychosocial. The latter group was without a doubt the largest, consisting of individuals who had spent their whole life wanting the same color eyes as their family members (parents and siblings with blue or green eyes while theirs are brown), or people subject to a social discrimination based on race, who saw this technique as the solution to the issue. In 95% of the cases, the patients came after many years of seeking information from the clinic, over the phone or via email, in patient forums, social networks, and through direct contact with the doctor. Therefore, they had comprehensive information, including a detailed informed consent, and the analyses in pre- and post-laser treatments. None of the cases were compulsive or poorly considered decisions.
Photoablative cosmetic iridoplasty (PCI) procedure
A detailed clinical history was gathered, especially focused on detecting exclusion criteria. If they were determined to be a good candidate, a general in-depth ophthalmologic examination was performed, as well as another specific one to PCI. We used the IRÎZ® (Eyecos) scanner and Analyzer program, which provided us with the data required to adequately plan the treatment: pigmentation grade, colorimetry, color contrast, iris pachymetry, and 3D topography. The scanner consists of three modules: photography (Topcon SL-D), optical coherence tomography (OCT Topcon SL-SCAN1) and pneumotonography (Reichert M30). The Analyzer IRÎZ (Eyecos) software also calculates the physio-dynamic parameters of the aqueous humor in the anterior chamber, which are indispensable for a safe technique: maximum intraocular pressure (IOP max), clearance curve (CC) and trabecular blockage factor (TBF). These data are shown in a simplified format in the Eyecos Iris Summary (Fig. 3).
After obtaining the Iris Summary (Eyecos), we used the Predictor IRÎZ software (Eyecos) to show the patient the expected results and their probability, based on the pigmentation of their eyes, skin, and hair, and that of their parents. This program is based on phenotype calculations according to the two genes law of eye color, in which a B allele (Brown) is dominant over a G allele (Green), which is in turn dominant over b (blue). By combining the variables, Predictor gives us the most probable option, as a percentage, followed by the second alternative. To achieve a realistic effect, the program offers real examples of eyes with similar characteristics that have been treated before. If the patients don’t know their parents (adoption or premature death), it is possible to perform a genetic test (Eyecos Color Biochip) using a saliva swab, which within a few weeks will give us a detailed report on their eye color genes, and the prediction of the results. The genetic test for open angle glaucoma is also available.
Afterward, we used the Simulator 3D IRÎZ software (Eyecos) to perform a 3D simulation of the patient’s eye and their most probable results. Furthermore, this program can simulate the effect that various lighting levels will have on the diameter of the pupil, as well as the influence of observation distance on the final color effect obtained. At this point, if the patient is considered eligible and has all the necessary information, they are required to sign the informed consent for PCI. After importing the Eyecos Iris Summary data from the Analyzer software, the Planner IRÎZ software (Eyecos) schedules each laser session and the different phases needed through treatment completion.
The medication prior to the procedure includes dexamethasone, tobramycin, and timolol maleate drops at 0.50% every 8 h starting two days before. As we have known for many years, the application of laser to the iris causes an inflammatory reaction similar to iritis, and laser depigmentation of the trabeculum in the SLT technique generates pressure peaks after its performance. To prevent both acute complications, previous therapy with topical anti-inflammatory and antihypertensive drugs is indicated. Tobramycin drops are associated just to prevent the appearance of conjunctival infection secondary to the repeated instillation of eye drops and excessive manipulation of the eyes during the 4 consecutive days that the PCI lasts, which would make it difficult to complete.
Without the routine administration of oral anxiolytics, anesthetic drops of tetracaine and oxybuprocaine are administered. If necessary, pilocarpine 2% drops can be applied to keep pupils miotic during the procedure. VOLK capsulotomy or iridectomy lenses are used, with methylcellulose drops, to fix the ocular globe and optimize focus in the iris.
All treatments were performed with the 532-nm Crystal Q-switched laser, with 3–4 ns pulses (commonly used in selective laser trabeculoplasty, or SLT). Models from different manufacturers were used (Ellex, Lightmed, Quantel Medical, Lumenis). The Planner software provides the parameters we must use according to the Analyzer software’s Iris Summary: power, duration, repetition frequency, number of shots, and treatment area. We follow the guidelines indicated by Planner until the specific area of the iris has been treated. The sessions tend to take no more than 5 min. The laser's effects are painless, although the light from the slit-lamp causes discomfort. Each phase consists of four or five consecutive daily sessions, which are repeated every 4–6 months until finalization, with the treatment completed in two or three phases.
Following the procedure, both steroidal and non-steroidal oral anti-inflammatories are prescribed, and the frequency of eye drops is increased to every hour for the first 5 h, and then every 2 h until midnight. Following the final session, the dose decreases to three times a day for only 1 week, and then we add artificial tears with sodium heparin every 8 h for 3 months. The topical anti-inflammatory and antihypertensive treatment lasts only one week, to avoid any type of discomfort. Its use does not affect the safety assessment of PCI since the statistical significance study is performed between the patient's previous values and those found in the medium and long term, when the patient no longer uses any topical treatment. Follow-up of visual acuity, refraction error, Goldmann eye pressure, biomicroscopy, HQ photography, and colorimetry study are carried out weekly, monthly and then every 4 months.
The patient is required to submit photographs of their eyes every 1–2 months using the Eye Selfie® (Eyecos) application to monitor their progress. Additionally, the patients receive an ocular examination in each phase, and the IRÎZ Scanner is used in order to calculate new Iris Summaries and allow comparison with previous progress. One function lets us automatically calculate the differences obtained in grade, colorimetry, contrast, pachymetry, topography and physio-dynamic parameters of the aqueous humor. In this way, patients are certified of the efficacy, safety, and predictability of the PCI through a written or digital report.
Data were collected independently by assistant optometrists and classified in database. Excel statistical program was used to perform a general descriptive study, calculation of correlation factors, and statistical significance analysis between quantitative variables (Student T Test).