A Prospective Study of Cyclosporine A 0.1% Combined with Loteprednol 0.2% vs Cyclosporine A 0.05% Alone in the Treatment of Dry Eye

Figures & data

Box 1 Exclusion criteria

Ocular surgery (eg, intraocular, oculoplastic, corneal, or refractive surgical procedure) performed within the last 3 months or at any time that in the investigator’s clinical judgment if it would interfere with the outcome measures of this study. Clinically significant ocular trauma. Active ocular herpes simplex or herpes zoster infection Ocular inflammation (uveitis, iritis, scleritis, episcleritis, keratitis, conjunctivitis) at the discretion of the investigator. Ocular infection (eg, viral, bacterial, mycobacterial, protozoan, or fungal infection or the cornea, conjunctiva, lacrimal gland, lacrimal sac, or eyelids, including hordeolum/stye). Active, systemic, or local disease condition that causes clinically significant ocular surface irritation such that it could interfere with the study findings. Moderate to severe (grade 2–4) allergic, vernal or giant papillary conjunctivitis. Severe (grade 3 or 4) inflammation of the eyelid (eg, blepharochalasis, staphylococcal blepharitis, or seborrheic blepharitis) Eyelid abnormalities that significantly affect the lid function (eg, entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, severe ptosis). Ocular surface abnormality that may compromise corneal integrity (eg, prior chemical burn, recurrent corneal erosion, corneal epithelial defect, grade 3 corneal fluorescein staining, map-dot-fingerprint dystrophy, or the effect of any other ophthalmic medication that might in the opinion of the investigator compromise the ocular surface integrity). Participation in this trial in the same patient’s fellow eye. Patients aged <18 years, pregnant or breastfeeding, or who may become pregnant during participation in the study.

Table 1 Enrollment by site

	Harvard Eye Associates (Hovanesian)	Cleveland Eye Clinic (Chester)	Inland Eye Specialists (Sorensen)	Combined
n	19	19	18	56
Age, years	69±5.7, range 61–85	56±17.0, range 24–79	67±9.7, range 50–82	64.0±12.9, range 24–85
Women	15 (79%)	16 (84%)	12 (67%)	43 (77%)
Right eye enrolled	12 (63%)	13 (68%)	8 (44%)	33 (61%)

Table 2 Enrollment by Treatment Group

	Cyclosporine–loteprednol	Cyclosporine	Combined	P
n	37	19	56
Age (years)	64.4±14.6, range 24–85	63.3±9.2, range 32–73	64±12.9, range 24 to 85	<0.77, (Student’s t-test)
Women	29 (78%)	14 (74%)	43 (77%)	<0.61 (^2 test)
Right eye enrolled	32 (86%)	11 (57%)	43 (77%)	<0.28 (^2 test)
Currently using lubricant drops	24 (65%)	15 (79%)	39 (70%)	<0.29 (^2 test)

Table 3 Significant improvements in total corneal higher order aberrations in the central 6 mm of the cornea were seen between baseline and each of week 2 and week 4 for the combination drop, while no significant improvement was seen for patients treated with cyclosporine alone

	Cyclosporine–loteprednol (n=37)		Cyclosporine (n=19)
Baseline	0.78±0.46 µm		0.78±0.82 µm
Week 2	0.64±0.36 µm	P<0.014 vs baseline, paired t-test	0.60±0.34 µm	P<0.18 vs baseline, paired t-test
Week 4	0.63±0.48 µm	P<0.012 vs baseline, paired t-test	0.78±0.74 µm	P<0.48 vs baseline, paired t-test

Figure 1 Significant improvements in HOAs were seen from baseline to week 2 and week 4 in eyes treated with the combination drop, whereas no significant change in HOAs was seen with cyclosporine.

Figure 2 Multifocal candidacy almost doubled among eyes receiving CsA–LE vs those taking CsA alone.

Figure 3 Both cyclosporine/–loteprednol and cyclosporine alone significantly reduced corneal staining (P<0.0001 for both drops for baseline vs 2 and 4 weeks, paired t-test).

Figure 4 Corneal staining improved significantly in both groups from baseline to both week 2 and 4 (P<0.00001, paired t-test for all comparisons).

Table 4 Mean tear-breakup time (TBUT) compared to baseline had improved significantly at each follow-up visit

	Baseline mean TBUT	Week 2 mean TBUT	Week 4 mean TBUT
Cyclosporine–loteprednol (n=37)	4.11±1.98	6.48±2.30 (P<0.0001)	6.37±5.86 (P<0.0001)
Cyclosporine (n=19)	4.05±2.07	8.58±5.78 (P<0.0005)	6.84±5.81 (P<0.0001)

Figure 5 The proportion of patients with an abnormally low TBUT (<5 seconds) decreased in all groups. This change was statistically significant for cyclosporine/–loteprednol at both 2 and 4 weeks (P<0.003 and <0.0001, respectively, McNemar’s ² test) and for cyclosporine at 4 weeks (P<0.01).

Table 5 Best-corrected visual acuity improved significantly between baseline and week 2 in patients taking CsA–LE, but not CsA alone, while no other differences were statistically significant

	Baseline	Week 2	Week 4
CsA–LE	0.17±0.15	0.13±0.15 (P<0.02 vs baseline, paired t-test)	0.13±0.19
CsA	0.13±0.16	0.08±0.15	0.15±0.21

Figure 6 Conjunctival redness (Schulze scale) improved significantly in both groups.

Figure 7 Frequency distribution of side effects of each medication.

Figure 8 Frequency of all side effects queried in the validated COMTOL questionnaire.

Table 6 IOP did not rise significantly in either group: abnormal pressure readings (>21 mmHg) were limited to a single patient (3%) in the combination drop group with an IOP of 30 MmHg at visit 3

	Baseline	Week 2	Week 4
Cyclosporine–loteprednol (n=37)	14.6±2.3, range 10–19	14.6±2.4, range 10–19 (P<0.47 vs baseline, paired t-test)	15.2±3.5, range 9–30 (P<0.11 vs baseline, paired t-test)
Cyclosporine (n=19)	14.03±2.5, range 11–21	14±3, range 10–19 (P<0.29 vs baseline, paired t-test)	13.2±2.6, range 9–19 (P<0.12 vs baseline, paired t-test)