The Impact of Systemic Light Chain Amyloidosis on Eyes (Amyloidosis)

The Impact of Systemic Light Chain Amyloidosis on Eyes and Its Appendages

Study Purpose and Principle: Amyloidosis is a group of diseases characterized by the deposition of amyloid proteins in tissues and organs throughout the body, with common affected organs including kidneys, heart, nervous system, gastrointestinal tract, and liver. Nowadays, nearly 40 different proteins have been found to form amyloid fibrils in body, among which Systemic Light Chain (AL) Amyloidosis is the most common type of systemic amyloidosis. AL amyloidosis is a plasma cell disorder, with its precursor protein originating from free light chains produced by abnormal plasma cell clones, which form amyloid substances that deposit in tissues and organs causing lesions. In terms of incidence, the incidence of AL amyloidosis is 8-10 cases per million person-years in the United States and is considered a rare disease in our country. AL amyloidosis has an insidious onset, diverse clinical manifestations, and is prone to misdiagnosis and missed diagnosis in clinical practice. The prognosis also has strong heterogeneity and is closely related to the extent of organ involvement at the time of diagnosis. In the past, the incidence of eye involvement in systemic AL amyloidosis patients was low, with various manifestations, only reported as case reports, and not regularly followed up with systemic treatment. Based on this, this project aims to assess the involvement of eyes and its appendages in patients with different stages of systemic light chain amyloidosis, with the goal of clarifying the ocular manifestations of this systemic disease and exploring early diagnostic indicators for the eye.

Primary Objective: To assess the involvement of the anterior segment of the eye, as well as the extraocular soft tissues and muscles, in patients with systemic light chain amyloidosis.

Secondary Objective: To assess the neuro-ophthalmic manifestations and changes in retinal choroidal blood flow in patients with systemic light chain amyloidosis.

Study Design: Observational study.

Study Population and Expected Enrollment: 80 patients with systemic light chain amyloidosis, 50 normal controls.

Study Duration: Six months of follow-up after the last subject is diagnosed and enrolled.

Intervention: Experimental Group: Patients with systemic light chain amyloidosis; Control Group: Subjects without systemic diseases.

Study Overview

• Status: Recruiting
• Conditions: Systemic Light Chain Amyloidosis; Ocular Complications

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Minglu Ma, Doctor; Phone Number: 86-13547891481; Email: mingluma@126.com
• Study Contact Backup: Name: yanjie yan; Phone Number: 020-66610729; Email: iacuc@gzzoc.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Zhongshan Opthalmic Center
      • Contact: yanjie yan; Phone Number: 020-66610729; Email: iacuc@gzzoc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Source and Selection Method of Case Group: Patients diagnosed with "Systemic Light Chain Amyloidosis" or suspected of having "Systemic Light Chain Amyloidosis" and treated according to relevant diagnostic and treatment standards at tertiary hospitals. They are planned to undergo ocular screening at Zhongshan Ophthalmic Center of Sun Yat-sen University to exclude ocular and adnexal complications. It is expected that 80 cases of systemic light chain amyloidosis will participate in this study.

Source and Selection Method of Control Group: Control group subjects are all sourced from the outpatient department of Zhongshan Ophthalmic Center of Sun Yat-sen University. It is expected that 50 cases of dry eye syndrome/cataract patients will participate in this study.

Description

Case Group

Inclusion Criteria:

1. Patients diagnosed with "Systemic Light Chain Amyloidosis";
2. No other severe systemic underlying diseases that affect the examination;
3. Subjects voluntarily participate in this study, sign the informed consent form;
4. Age between 18-80 years old, no gender restrictions.

Exclusion Criteria:

1. Patients with eye diseases of clear causes such as ocular surface malignant tumors, corneal perforation, severe eye trauma, etc.;
2. Patients with nystagmus;
3. Severe ocular scar diseases; conjunctival scars with fornix shortening;
4. Current signs of infection, including fever and undergoing antibiotic treatment;
5. Mental abnormalities;
6. Pregnant or breastfeeding women, or women planning to become pregnant within 2 years;
7. NYHA Class IV: Heart disease patients cannot engage in any physical activity, with heart failure symptoms even at rest, and worsening with physical activity;
8. NT-proBNP > 8,500 ng/L.

Control Group

Inclusion Criteria:

1. Stable general condition, not patients with "Systemic Light Chain Amyloidosis";
2. No other severe systemic underlying diseases that affect the examination;
3. Subjects voluntarily participate in this study, sign the informed consent form;
4. Age between 18-80 years old, no gender restrictions.

Exclusion Criteria:

1. Patients with eye diseases of clear causes such as ocular surface malignant tumors, corneal perforation, severe eye trauma, etc.;
2. Patients with nystagmus;
3. Severe ocular scar diseases; conjunctival scars with fornix shortening;
4. Current signs of infection, including fever and undergoing antibiotic treatment;
5. Mental abnormalities;
6. Pregnant or breastfeeding women, or women planning to become pregnant within 2 years.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Exposed group; Exposed group: Ocular Complications of Systemic Light Chain Amyloidosis. Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Unexposed group; Unexposed group: patients without Systemic Light Chain Amyloidosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival Mass	Conjunctival Mass: The size of the yellowish-pink waxy mass on the bulbar or palpebral conjunctiva (if present, additional conjunctival confocal microscopy examination is performed to clarify the microscopic morphology of the mass).	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Subconjunctival Hemorrhage Grading	Subconjunctival Hemorrhage: No conjunctival congestion is scored 0; mild diffuse conjunctival congestion is scored 1; moderate diffuse conjunctival congestion, with noticeable congestion near the fornices, is scored 2; severe diffuse conjunctival congestion with subconjunctival hemorrhage is scored 3.	Each system light chain amyloidosis patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periocular Purpura	Purple-red macules and papules on the skin around the orbit.	Each system light chain amyloidosis patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Ptosis	Measure the degree to which the upper eyelid margin covers the cornea when both eyes are open and looking straight ahead. It is classified based on the degree of coverage: Mild: Coverage ≤4 mm, with a drooping amount of ≤2 mm; Moderate: Coverage >4～≤6 mm, drooping amount >2～≤4 mm; Severe: Coverage >6 mm, reaching the central part of the pupil, with a drooping amount >4 mm.	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Vitreous Opacity	Fundus photography records the morphology of vitreous opacity, such as Weiss ring, flocculent, dense membranous, fine punctate, filamentous, reticular, etc.	Each system light chain amyloidosis patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Cup-to-Disc Ratio (C/D)	After mydriasis (pupil > 6 mm), in a dark room, a skilled professional technician uses a digital fundus camera to adjust the machine's height, the subject's head position, and seating. The subject is instructed to open their eyes and focus on the cursor inside the machine, and two directional fundus photographs are taken for each eye (centered on the macula and the optic disc, respectively).	Each system light chain amyloidosis patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Visual Field	The extent of visual field defects is assessed according to the HPA (Humphrey Perimetry Analysis) international visual field staging method. An average deviation of <-6dB is considered mild, -6dB ≤ average deviation ≤ -12dB is moderate, and an average deviation >-12dB is severe.	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Retinal Microvasculature	OCTA measurement of superficial retinal vessel density in the foveal center (3mm)	Each system light chain amyloidosis patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Retinal Nerve Fiber Layer Thickness	Heidelberg OCT measurement of retinal nerve fiber layer thickness in the foveal center (6mm)	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Choroidal Thickness	Heidelberg OCT measurement of choroidal thickness in the foveal center (6mm)	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Cornea	Corneal Dystrophy: Mucous drop dystrophy and lattice dystrophy of the cornea. If present, anterior segment OCT (Optical Coherence Tomography) is performed to assist in determining the depth of corneal opacity and deposition.	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Visual Acuity	Uncorrected distant visual acuity is assessed using a Snellen chart. If the uncorrected distant visual acuity is less than 1.0, additional tests including computerized refraction and corrected distant visual acuity are performed.	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.
Non-contact Intraocular Pressure	The tonometer measures the intraocular pressure and displays the result on the screen, taking three consecutive measurements. If an erroneous value is detected, the subject rests and adjusts for 1 minute before repeating the intraocular pressure measurement three times to record the accurate data.	Each patient will be followed up once every 2 months, for a total of 4 follow-ups, over a 6-month period, to observe any ocular complications and progression.

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University
• Investigators: Principal Investigator: chang he, Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2024
• Primary Completion (Estimated): August 13, 2026
• Study Completion (Estimated): August 13, 2026

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: January 26, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 26, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Systemic Light Chain Amyloidosis; Ocular Complications
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: 2024KYPJ080; 82322016 (Other Grant/Funding Number: National Natural Science Foundation of China Outstanding Young Scientists Fund Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No