Clinical trial NCT05278169: Central Serous Chorioretinopathy Registry and Pachychoroid Observation and Natural History Study
Official title: Central Serous Chorioretinopathy Registry and Pachychoroid Observation and Natural History Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Central Serous Chorioretinopathy
Keywords: Central Serous Chorioretinopathy
Pachychoroid
Optical Coherence Tomography
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-03-14
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study aims to enrol a total of 350 patients with CSCR, of which:

* 170 subjects from a previous cross-sectional observation study titled 'The Association of Sleep Disturbances and Maculopathy' (IRB / REC No.: 2018.158) at the CUHK Eye Centre.
* An addition of 180 subjects will be recruited during the proposed study duration. Of the 180 new recruits, 100 will be recruited from Hong Kong Eye Hospital and CUHK Eye Centre.The remaining 80 subjects will be recruited from Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital.

Brief summary: Objectives:

1. To conduct a Natural History Observation Study to characterize the clinical features and progression of Central Serous Chorioretinopathy (CSCR) from the earliest to the vision-threatening stages.
2. Collect genetic samples of affected individuals and their families to establish whether there is a genetic basis for the disease.
3. To create a Registry of patients affected by CSCR who may agree to be contacted for inclusion in future clinical trials.
4. To determine the incidence and risk factors for progression of pachychoroid phenotypes identified from the unaffected fellow eyes of CSCR patients.

Design and subjects:

Observation, non-interventional study with prospective follow-up for 2 years. The study aims to enroll 350 patients with CSCR (100 from Hong Kong Eye Hospital, 80 from Prince of Wales Hospital and Alice Ho Miu Ling Nethersole Hospital, and 170 from Chinese University of Hong Kong (CUHK) Eye Centre at Hong Kong Eye Hospital).

Study instruments:

Functional tests include visual acuity and microperimetry. Retinal imaging with non-invasive ultra-widefield colour fundus camera, fundus autofluorescence (FAF) and optical coherence tomography (OCT). Questionnaires for risk factor profiling and quality of life assessment. Blood specimen will be collected for genetic testing if found to have a clinical diagnosis of CSCR as determined at CUHK Eye Centre at Hong Kong Eye Hospital.

Main outcome measures:

The primary outcome will be longitudinal alteration of retinal pigment epithelium defects on FAF, spectral domain (SD) OCT and infrared imaging. The secondary outcomes are: 1) progressive attenuation of outer nuclear layer (ONL), external limiting membrane (ELM) and ellipsoid zone (EZ) on SD OCT, 2) longitudinal changes of subfoveal choroidal thickness on swept source (SS) OCT, 3) incidence and onset of intraretinal cysts, 4) incidence and onset of type 1 choroidal neovascularization, 5) rate of choriocapillaris non- perfusion on SS OCT angiography (OCTA), 6) rate of loss of retinal sensitivity using microperimetry tests, 7) rate of visual acuity loss, 8) epidemiology of risk factors associated with CSCR, 9) identification of genes and the genetic variants that are associated with susceptibility to CSCR and 10) documentation of the clinical course of serous retinal detachment recurrence(s), persistence and resolution.

Detailed description: Significance and Applications of Study Results:

I) The proposed study will determine comprehensive clinical characterization of a large cohort of 350 CSCR patients with novel, non-invasive imaging techniques to examine the ultrastructure of the choroid and retina to detect subtle changes that are not visible through routine eye check and conventional fundoscopy examination.

II) To understand the pathophysiology of CSCR through studying ultrastructural changes of chorioretina and genotypes.

III) Longitudinal data from this study will determine CSCR progression risks and treatment outcomes. Our large CSCR database will be a unique, large cohort study with robust clinical and molecular characterizations. This knowledge could help to develop realistic and effective diagnostic tests and individualized treatments for CSCR, and aid in the design of future clinical trials.

Data analysis:

Statistical analyses will be conducted using standard statistical software (SPSS, STATA). The investigators will use a variety of statistical techniques for analysis. Unless otherwise specified, all statistical tests will be two-sided with a 0.05 level of significance. All confidence intervals will be two-sided with 95% confidence level. Categorical variables will be presented as the number and percentage of patients in each category. Continuous variables will be summarized using descriptive statistics such as n, mean, standard deviation, median, minimum, and maximum.

Descriptive statistics will be provided for patient demographics and baseline characteristics. Other relevant baseline information will be listed and summarized as appropriate with descriptive statistics.

An independent committee will review the data and safety of the study. Adequate records will be maintained and made available for audit / inspection. All study documents will be kept for a period of at least three years after study closure.

Significant Differences from Usual Management:

1. The study is a prospective natural history observation study and the protocol requires a total of 5 visits (in addition to routine care) to the CUHK Eye Centre at Hong Kong Eye Hospital for a duration of 2 years.
2. Blood taking will only be performed during the first (baseline) visit for genetic study.

Methods:

For Visit 1 (Baseline, Month 0):

1. Demography and Past medical history (1.1. Medical history, 1.2. Drugs history, 1.3. Blood pressure (BP) and Body-mass index (BMI) measurements, 1.4. Previous fluorescein and indocyanine green angiography images (if available) will be reviewed)
2. Visual function, intraocular pressure and ocular biometry (2.1. Best corrected visual acuity, 2.2. Autorefraction, 2.3. Axial length measurement, 2.4. Fundus Autofluorescence, 2.5. Macular Spectral Domain Optical Coherence Tomography (SD-OCT) 2.6. Ultra-widefield color fundus photography and autofluorescence, 2.7. Macular Swept Source Optical Coherence Tomography (SS-OCT), 2.8. OCT angiography, 2.9. Microperimetry)
3. Sleep quality, mood and quality of life questionnaires (3.1. Morningness and Eveningness Questionnaire, 3.2. Pittsburgh Sleep Quality Index (PSQI), 3.3. Insomnia Severity Index (ISI), 3.4. Epworth Sleepiness Scale (ESS), 3.5. General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) questionnaires, 3.6. National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25) quality of life questionnaire)
4. Blood taking for genetic study

For Visit 2 (Month 6) to Visit 5 (Months 24):

1.1 to 1.4 will be reviewed for any updates. The eye investigations that will be repeated are: 2.1, 2.4 - 2.9 The questionnaires that will be repeated are: 3.5 - 3.6 (only during Visits 3 and 5)

Eligibility criteria: Inclusion Criteria:

* Presence or evidence of prior serous retinal detachment documented on OCT involving the posterior pole unrelated to another disease process.
* At least 1 area of retinal pigment epithelium (RPE) alteration on FAF, SD-OCT, or infrared imaging.
* Subfoveal choroidal thickness (SFCT) of 300μm or more on SD enhanced depth imaging (EDI) OCT or SS-OCT for at least one eye.
* Patient 18 years or older.
* Willing to undergo pupil dilation, and protocol-required procedures for both eyes.

Exclusion Criteria:

* Other maculopathy on clinical examination such as age-related macular degeneration (AMD).
* Media opacity such as cataract that could interfere with adequate acquisition of fundal images.
* Pregnant or nursing women.

Primary outcomes:
measure: Longitudinal change of retinal pigment epithelium defects on Fundus Autofluorescence (FAF) from baseline and between visits.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Longitudinal change of retinal pigment epithelium defects on Spectral Domain Optical Coherence Tomography (SD-OCT) from baseline and between visits.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Longitudinal change of retinal pigment epithelium defects on infrared imaging from baseline and between visits.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
Secondary outcomes:
measure: Progressive attenuation of outer nuclear layer (ONL), external limiting membrane (ELM) and ellipsoid zone (EZ) on SD-OCT.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Changes of subfoveal choroidal thickness on swept source optical coherence tomography (SS-OCT).
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Incidence of intraretinal cysts.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Onset of intraretinal cysts.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Incidence of type 1 choroidal neovascularization.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Onset of type 1 choroidal neovascularization.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Changes of choriocapillaris non-perfusion on SS OCT angiography (OCTA).
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Changes of retinal sensitivity using microperimetry tests.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Visual acuity changes.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of medical history with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of oral corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of intravenous corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of intravitreal corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of periocular corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of intranasal corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of intra-articular corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of epidural corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of dermal corticosteroids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of antacids with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of antihistamines with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of nasal sprays that contain pseudoephedrine and oxymetazoline with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of use of phosphodiesterase-5 inhibitors with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of blood pressure (BP) with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of body-mass index (BMI) with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of previous findings in fluorescein and indocyanine green angiography images with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of best corrected visual acuity with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of autorefraction with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of axial length measurement with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of findings in Fundus Autofluorescence with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of findings in Macular Spectral Domain Optical Coherence Tomography (SD-OCT) with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of findings in ultra-widefield color fundus photography and autofluorescence with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of findings in Macular Swept Source Optical Coherence Tomography (SS-OCT) with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of findings in OCT angiography with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of findings in microperimetry with CSCR.
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
measure: Epidemiological association of morningness - eveningness choronotype with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of sleep quality with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of severity of insomnia with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of excessive daytime sleepiness with CSCR.
timeFrame: At baseline (Month 0).
measure: Epidemiological association of anxiety with CSCR.
timeFrame: At baseline (Month 0), Month 12 and Month 24.
measure: Epidemiological association of depression with CSCR.
timeFrame: At baseline (Month 0), Month 12 and Month 24.
measure: Epidemiological association of quality of life with CSCR.
timeFrame: At baseline (Month 0), Month 12 and Month 24.
measure: Association of single nucleotide polymorphism (SNP) with susceptibility to CSCR
timeFrame: At baseline (Month 0).
measure: Number of Participants with serous retinal detachment
timeFrame: At baseline (Month 0), Month 6, Month 12, Month 18 and Month 24.
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: CUHK Eye Centre
city: Hong Kong
country: Hong Kong
facility: Hong Kong Eye Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Danny Siu-Chun Ng, FHKAM(Ophth)
role: PRINCIPAL_INVESTIGATOR
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