Clinical trial NCT05850936: Effect of IOP Lowering on Progressive HM
Official title: Effect of Medically Intraocular Pressure Lowering on Progressive High Myopia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: High Myopia
Intraocular Pressure
Keywords: high myopia
intraocular pressure
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-05-09
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, single-center, randomized controlled trial
Primary purpose: PREVENTION

Brief summary: Currently, whether and when intraocular pressure (IOP) lowering medication should be used in progressive high myopia (HM) to control axial elongation is still a dilemma. Randomized trials are required to evaluate whether IOP lowering influences the growth of axial length in progressive HM eyes.

Detailed description: Myopia has emerged as a major health issue in east Asia, especially the sight-threatening complications associated with high myopia (HM). Complication of HM can be associated with significant ocular morbidities including maculopathy, retinal detachment, and glaucoma.

Previous studies have shown that adult patients with HM have sustained growth of the axial length (AL), which is a risk factor for the progression of pathological myopia and thus may further affect the visual function , so how to slow down the sustained growth of the AL in adult patients with HM has become an urgent clinical problem. Previous studies have shown that IOP-lowering treatment is a protective factor for the growth of the AL in HM , and the results of animal experiments have further shown that medically IOP-lowering treatment can significantly slow down the AL lengthening and refractive changes in the guinea pig model of myopia. On this basis, the investigators proposed in a previous article that medically IOP-lowering treatment may slow down the growth of AL by three pathways related to the sclera and choroid: for the sclera, IOP-lowering treatment may reduce the scleral distending force, slow down the rate of scleral distension, and inhibit the activation of scleral fibroblasts to reduce scleral remodeling; for the choroid, IOP-lowering treatment may increase choroidal blood perfusion and for the choroid, hypotensive treatment can increase choroidal perfusion and thus reduce scleral remodeling due to scleral hypoxia. A previous retrospective study conducted by the investigators also shows that medically IOP-lowering treatment could control the progression of AL in HM, but there is still a lack of evidence from relevant robust randomized controlled clinical trials (RCT).

The investigators propose to conduct a RCT to evaluate whether medically IOP-lowering therapy is effective in controlling the progression of AL in HM. Secondly, this study also aims to provide data to evaluate IOP-lowering treatment effects on the incidence of changes in the visual field (VF), optic nerve head morphology including the retinal nerve fiber layer (RNFL), and retinal ganglion cell-inner plexiform layer (GC-IPL) loss, progression of myopic maculopathy, loss in visual function and change in quality of life. The outcomes of this study may provide a strong basis for treatment recommendations to control the progression of high myopic eyes, and to provide high-quality clinical research evidence for international clinical guidelines on myopia.

Eligibility criteria: Inclusion Criteria:

1. Informed consent given, and consent form signed.
2. Age between 18 and 65 years.
3. Diagnosed with HM: spherical equivalent ≤ -6.00 diopters or AL ≥ 26.5 mm.
4. Progressive HM: progression in AL ≥0.05mm in the past 6 months or ≥0.1mm in the past 12 months.
5. IOP ≥ 10 mmHg and ≤ 21mmHg on at least 2 visits, as measured by Goldmann applanation tonometry .
6. Best corrected visual acuity (BCVA) ≥ 6/12, and being able to obtain adequate AL examination, fundus photographs, optical coherence tomography (OCT) and complete the VF examination.

Exclusion Criteria:

1. Allergic to any kind of IOP-lowering therapy.
2. Combination of various serious fundus pathologies, such as proliferative diabetic retinopathy, retinal detachment, central retinal artery occlusion, etc.
3. Combination of chronic, recurrent or severe ocular inflammatory lesions, such as chronic or recurrent uveitis.
4. Patients with significant corneal or iris lesions, or severe cataract affecting fundus examination, or patients with only one eye.
5. Patients who have undergone any surgery or laser treatment affecting eye parameters during the follow-up period (within the last 1 year), such as cataract surgery.
6. Patients with other serious systemic diseases, such as hypertension, heart disease, diabetes, rheumatic immune system disease, etc., who cannot tolerate long-term follow-up and eye treatment.
7. Pregnant or lactating women, or those who plan to have children during the follow-up period.

Primary outcomes:
measure: progression of axial length (AL)
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of visual field (VF) defects or progression
timeFrame: 12 months
measure: Incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)
timeFrame: 12 months
measure: progression of myopic maculopathy
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Xiulan Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leske MC, Hyman L, Hussein M, Heijl A, Bengtsson B. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1999 May;127(5):625-6. No abstract available.
citation: Garway-Heath DF, Crabb DP, Bunce C, Lascaratos G, Amalfitano F, Anand N, Azuara-Blanco A, Bourne RR, Broadway DC, Cunliffe IA, Diamond JP, Fraser SG, Ho TA, Martin KR, McNaught AI, Negi A, Patel K, Russell RA, Shah A, Spry PG, Suzuki K, White ET, Wormald RP, Xing W, Zeyen TG. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Apr 4;385(9975):1295-304. doi: 10.1016/S0140-6736(14)62111-5. Epub 2014 Dec 19.
citation: Leske MC, Heijl A, Hyman L, Bengtsson B. Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999 Nov;106(11):2144-53. doi: 10.1016/s0161-6420(99)90497-9.