Ophthalmic Research – Ken WU

WU Zhongheng Ken

 

Qualification:

  • BMed, Tongji Medical College, Huazhong University of Science and Technology

Research Areas:

  1. Longitudinal deformation of optic nerve head surface and anterior laminar cribrosa surface in glaucoma patients and their associated risk factors
  2. Longitudinal deformation of Bruch’s Membrane opening associated with optic nerve head surface and anterior laminar cribrosa surface
  3. Rates of change of optic nerve head surface and anterior laminar cribrosa surface and their impact on visual field progression

Supervisor:

Publications:

  1. Wu Z, Xu G, Weinreb RN, Yu M, Leung CK. Optic Nerve Head Deformation in Glaucoma: A Prospective Analysis of Optic Nerve Head Surface and Lamina Cribrosa Surface Displacement. Ophthalmology.2015 Jul;122(7):1317-29.
  2. Zhongheng Wu, Guihua Xu, Robert N Weinreb, Sayantan Biswas, Marco Yu, Christopher KS Leung. Optic Nerve Head Deformation in Glaucoma: Association with Longitudinal Changes of Bruch’s Membrane Opening. Manuscript under revision.
  3. Zhongheng Wu, Chen Lin, Michael Crowther, Christopher KS Leung. Optic Nerve Head Deformation in Glaucoma: Rates of Change of ONH and Lamina Cribrosa Surface Depths Impact Visual Field Progression. Manuscript pending submission.

 

Research Highlights:

(1) Optic Nerve Head Deformation in Glaucoma: A Prospective Analysis of Optic Nerve Head Surface and Lamina Cribrosa Surface Displacement

Study of the optic nerve head structures, including the lamina cribrosa is relevant to understanding the mechanisms of retinal ganglion cell degeneration in glaucoma and devising new diagnostic and therapeutic strategies. Current knowledge of deformation of the ONH and anterior LC surfaces in glaucoma is primarily derived from modeling and experimental studies. In this study, using the spectral-domain optical coherence tomography which affords reliable measurement of the optic nerve head surface depth and anterior lamina cribrosa surface depth, we aim to investigate whether displacement of the ONH and LC surfaces can be observed clinically with serial measurements during the course of glaucoma progression, additionally whether such displacement would be anterior or posterior. We founded that the ONH and ALC surfaces displaced not only posteriorly but also anteriorly in a significant portion of glaucoma patients, and for each millimeter of mercury increase in the average intraocular pressure during follow-up, the ONH and ALC surfaces displaced posteriorly by 1.6 μm and 2.0 μm, respectively while an older age was associated with a decrease in magnitude of posterior displacement of the ONH and anterior laminar surfaces.

 

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Figure 1. An optical coherence tomography (OCT) optic disc image (A) for measurement of the optic nerve head surface depth (ONHSD) (B), anterior lamina cribrosa surface depth (ALCSD) (C), and prelaminar tissue thickness (PTT) (D) after manual detection of the Bruch’s membrane opening (BMO) (pink dots), internal limiting membrane/ONH surface (green), and anterior lamina cribrosa (LC) surface (orange). The reference line (pink) is a line joining the BMO. The ONHSD represents the perpendicular distances from the reference line to the ONH surface (the blue lines are for illustrative purpose and do not represent all the lines the software measured). The ALCSD represents the perpendicular distances from the reference line to the anterior LC surface. The PTT represents the distance between the ONH and the anterior LC surfaces. The retinal pigment epithelium/Bruch’s membrane is highlighted in red.

 

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Figure 2. An example demonstrating posterior displacement of the optic nerve head (ONH) and anterior lamina cribrosa (LC) surfaces in a glaucomatous eye followed from January 10, 2010, to March 21, 2014. The scanning laser ophthalmoscopy image and optical coherence tomography (OCT) images of the vertical meridian (with and without tracing of the reference line [pink], ONH [green], and anterior LC [orange] surfaces) at the baseline (A) and latest (B) follow-up visits are shown. The ONH and the anterior LC surfaces displaced posteriorly by 38.3 μm and 53.2 μm, respectively. The prelaminar tissue thickness (PTT) decreased by 31.9 μm. The average intraocular pressure (IOP) and the standard deviation of IOP during the follow-up were 25.5 mmHg and 5.5 mmHg, respectively.

 

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Figure 3. An example demonstrating anterior displacement of the optic nerve head (ONH) and anterior lamina cribrosa (LC) surfaces in a glaucomatous eye followed from February 9, 2009, to October 18, 2013. The scanning laser ophthalmoscopy image and optical coherence tomography (OCT) images of the vertical meridian (with and without manual tracing of the reference line [pink], ONH [green], and anterior LC [orange] surfaces) at the baseline (A) and latest (B) follow-up visits are shown. The ONH and the anterior LC surfaces displaced anteriorly by 41.0 μm and 59.3 μm, respectively. The prelaminar tissue thickness (PTT) did not show a significant change. The average intraocular pressure (IOP) and the standard deviation of IOP during the follow-up were 20.1 mmHg and 1.3 mmHg, respectively.

 

(2) Optic Nerve Head Deformation in Glaucoma: Association with Longitudinal Changes of Bruch’s Membrane Opening

The neural canal, extending from the Bruch’s membrane opening (BMO) to the posterior scleral canal opening, represents a conduit through which the axons of retinal ganglion cells transit through the eyeball. Findings of the BMO change from previous experimental and clinical studies are divided. While the discrepancies among the studies can be in part attributed to the differences in the instruments as well as the landmarks for measurement of neural canal opening, the ability is limited of cross-sectional studies to determine whether the NCO enlarges or contracts over time. In this study, we aim to addreass whether the NCO expands or contracts at the level of Bruch’s membrane, and its association with LC deformation, as glaucoma progresses. We found BMO not only widened, but also narrowed with time in glaucoma patients. In general, posterior LC deformation was associated with widening of the BMO; anterior LC deformation was associated with narrowing of the BMO. And the relationship between change in BMOW and change in ALSD was significantly influenced by age and IOP SD and it changed from a positive to a negative association with decreasing age (<33.9 years) and increasing IOP SD (>4.8mmHg).

 

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Figure 4. A figure showing the relationship between BMOW and ALCSD changed from a negative to a positive association with increasing age at age of 33.9 years.

 

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Figure 5. A figure showing the relationship between BMOW and ALCSD changed from a negative to a positive association with decreasing IOP SD at an IOP SD of 4.8 mmHg.

 

(3) Optic Nerve Head Deformation in Glaucoma: Rates of Change of ONH and Lamina Cribrosa Surface Depths Impact Visual Field Progression

Proposed as the primary site of axonal injury in glaucoma through deformation which may precede axonal damage and decline in visual function in glaucoma, Lamina cribrosa is becoming an attractive target to investigate the development and progression of glaucoma since LC has been. However clinical documentations of ONH deformation parameters including anterior lamina cribrosa surface depth (ALCSD) and ONH surface depth (ONHSD) are rarely found in clinical practice. In this study, we hypothesize that progressive deformation of the anterior LC and ONH surfaces represents an early biomarker in the continuum of glaucoma progression and that the rates of change of ALCSD and ONHSD would predict functional decline in glaucoma patients. We found that there was a wide variation in the rates of change of ALCSD/ONHSD in glaucoma which were influenced by age, baseline ALCSD/ONHSD measurements and visit-to-visit variation in IOP. Identifying individual eyes with a rapid rate of posterior ALCS and ONHS deformation is pertinent to glaucoma management as they exhibit a higher risk of development of VF progression.

 

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Figure 6. A figure showing two examples of conditional survival predictions one with and another without visual field progression extended from the joint longitudinal and survival modeling, visualizing the association between the longitudinal profiles of ALCSD and visual field survival probability.