A technique called optical coherence tomography (OCT) has been developed for noninvasive cross-sectional imaging in biological systems. OCT uses low-coherence interferometry to produce a two-dimensional image of optical scattering from internal tissue microstructures in a way that is analogous to ultrasonic pulse-echo imaging. OCT has longitudinal and lateral spatial resolutions of a few micrometers and can detect reflected signals as small as approximately 10(-10) of the incident optical power. Tomographic imaging is demonstrated in vitro in the peripapillary area of the retina and in the coronary artery, two clinically relevant examples that are representative of transparent and turbid media, respectively.

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Optical coherence tomography

Aim: To estimate the number of people with open angle (OAG) and angle closure glaucoma (ACG) in 2010 and 2020. Methods: A review of published data with use of prevalence models. Data from population based studies of age specific prevalence of OAG and ACG that satisfied standard definitions were used to construct prevalence models for OAG and ACG by age, sex, and ethnicity, weighting data proportional to sample size of each study. Models were combined with UN world population projections for 2010 and 2020 to derive the estimated number with glaucoma. Results: There will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG. Women will comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma in 2010. Asians will represent 47% of those with glaucoma and 87% of those with ACG. Bilateral blindness will be present in 4.5 million people with OAG and 3.9 million people with ACG in 2010, rising to 5.9 and 5.3 million people in 2020, respectively. Conclusions: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians.

The number of people with glaucoma worldwide in 2010 and 2020

Optical coherence tomography (OCT) has developed rapidly since its first realisation in medicine and is currently an emerging technology in the diagnosis of skin disease. OCT is an interferometric technique that detects reflected and backscattered light from tissue and is often described as the optical analogue to ultrasound. The inherent safety of the technology allows for in vivo use of OCT in patients. The main strength of OCT is the depth resolution. In dermatology, most OCT research has turned on non-melanoma skin cancer (NMSC) and non-invasive monitoring of morphological changes in a number of skin diseases based on pattern recognition, and studies have found good agreement between OCT images and histopathological architecture. OCT has shown high accuracy in distinguishing lesions from normal skin, which is of great importance in identifying tumour borders or residual neoplastic tissue after therapy. The OCT images provide an advantageous combination of resolution and penetration depth, but specific studies of diagnostic sensitivity and specificity in dermatology are sparse. In order to improve OCT image quality and expand the potential of OCT, technical developments are necessary. It is suggested that the technology will be of particular interest to the routine follow-up of patients undergoing non-invasive therapy of malignant or premalignant keratinocyte tumours. It is speculated that the continued technological development can propel the method to a greater level of dermatological use.

https://link.springer.com/content/pdf/bfm%3A978-3-319-06419-2%2F1.pdf

Optical Coherence Tomography

AIM: To estimate the prevalence of glaucoma among people worldwide. METHODS: Available published data on glaucoma prevalence were reviewed to determine the relation of open angle and angle closure glaucoma with age in people of European, African, and Asian origin. A comparison was made with estimated world population data for the year 2000. RESULTS: The number of people with primary glaucoma in the world by the year 2000 is estimated at nearly 66.8 million, with 6.7 million suffering from bilateral blindness. In developed countries, fewer than 50% of those with glaucoma are aware of their disease. In the developing world, the rate of known disease is even lower. CONCLUSIONS: Glaucoma is the second leading cause of vision loss in the world. Improved methods of screening and therapy for glaucoma are urgently needed.

https://bjo.bmj.com/content/bjophthalmol/80/5/389.full.pdf

Number of people with glaucoma worldwide.

Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.

High Efficiency Transfection of Rat Retinal Ganglion Cells by a Modified Adeno-associated Virus Incorporating the Woodchuck Hepatitis Post-transcriptional Regulatory Element

Retinal ganglion cell (RGC) replacement and optic nerve regeneration hold potential for restoring vision lost to optic neuropathy. Following transplantation, RGCs must integrate into the neuroretinal circuitry in order to receive afferent visual signals for processing and transmission to central targets. To date, the efficiency of RGC retinal integration following transplantation has been limited. We sought to characterize spontaneous interactions between transplanted human embryonic stem cell-derived RGCs and the recipient mature mammalian retina, and to identify and overcome barriers to the structural integration of transplanted neurons. Using an in vitro model system, following transplantation directly onto the inner surface of organotypic mouse retinal explants, human RGC somas form compact clusters and extend bundled neurites that remain superficial to the neural retinal tissue, hindering any potential for afferent synaptogenesis. To enhance integration, we explored methods to increase the cellular permeability of the internal limiting membrane (ILM). Digestion of extracellular matrix components using proteolytic enzymes was titrated to achieve disruption of the ILM while minimizing retinal toxicity and preserving endogenous retinal glial reactivity. Such ILM disruption is associated with dispersion rather than clustering of transplanted RGC bodies and neurites, and with a marked increase in transplanted RGC neurite extension into retinal parenchyma. The ILM appears to be a barrier to afferent retinal connectivity by transplanted RGCs and its circumvention may be necessary for successful functional RGC replacement through transplantation.

/pdf/structural-engraftment-and-topographic-spacing-of-19zbbdbtjb.pdf

Structural engraftment and topographic spacing of transplanted human stem cell-derived retinal ganglion cells

CNTF Over-Expression Leads to Increased Retinal Ganglion Cell Survival in Experimental Glaucoma

Our recent publication noted several features of change in anterior lamina depth (ALD) with change in intraocular pressure (IOP) in glaucoma patients. ALD changed more in the lower ranges of IOP than at higher ranges, which represents the expected increased stiffening of biomaterials in regions of higher stress. Some eyes exhibited movement of the lamina out of the eye at lower IOP—a behavior that is more likely when the peripapillary sclera is more compliant. This was more common in eyes with less glaucoma damage. The regions of the lamina that moved more were in its vertical poles, above and below, as suggested by the lower density of connective tissue in the lamina there. Within an individual optic nerve head (ONH), there was greater displacement with IOP change in clock hours that retained more normal nerve fiber layer in the corresponding peripapillary nerve fiber layer. Compliance of ALD may be a relevant and practical biomarker for glaucoma susceptibility by noninvasive imaging. None of these findings are affected by the issue discussed in the Letter to the Editor. The letter by Rebolleda et al. discusses the reference plane for images in optical coherence tomography (OCT) of the optic nerve head. In past work in this field, Bruch’s membrane opening (BMO) has been the standard reference plane, and our paper used it as well, both for consistency with the literature and because we recognize that it is the best of three alternatives: BMO, choroidal–scleral interface (CSI), or RPE. The reasons that BMO position is the best reference are as follows: (1) it is visible in 100% of scans; (2) it can be detected by automated software without human ‘‘marking’’; (3) it does not change in size or shape with moderate shifts in IOP (documented in our paper); and (4) the putative change in its position with IOP change due to choroidal thickness change as suggested by Rebolleda et al. is not a significant issue. It is important to distinguish choroidal thickness in the immediate peripapillary area from that of the choroid underlying the macula. Rebolleda et al. refer to choroidal thickness changes in two cited references (their references 6 and 7), but these investigations (one of them by our group) studied change in choroidal thickness with IOP change in the macular area, not near the disc. The peripapillary choroid tapers down to become much thinner in most eyes directly underlying the edge of BMO. Therefore, the change in BMO position at that site due to choroidal thickness change is trivially small compared with the hundreds of micrometers of movement that we measured in ALD with change in IOP. Any movement of BMO due to change in the thin choroid at the disc margin is within the margin of error on repeat measurements at the same IOP. Likewise, using a choroidal thickness measurement 3.5 mm from the disc center, as Rebolleda et al. did, is not ‘‘peripapillary’’ and is not indicative of change in choroidal thickness immediately under the edge of BMO. The weaknesses of using the CSI as reference are many. (1) As we and others have published, 20% of eyes have no clearly identifiable CSI using present technology. (2) The position of CSI has not been accurately automated and its subjective marking by human observers has a variance vary far greater than any putative movement of BMO. (3) CSI is not a smooth curve, so that selecting one arbitrary location along it (as Rebolleda et al. have done) can give rise to significant variability from image to image. (4) The eye changes in axial length and curvature at the CSI with IOP change, so the claim that it is ‘‘better’’ ignores the fact that CSI is equally and potentially more mobile with IOP change than BMO. (5) In some eyes, the CSI reference position chosen by Rebolleda et al. (3.5 mm from the disc center) leads to a reference line that practically runs right through the anterior lamina border, making its depth essentially zero when it clearly is posterior to the BMO inlet. In these eyes, a CSI reference plane would (artifactitiously) produce huge changes in ALD as a percent of baseline. (6) We measured and published choroidal thickness change in the macular zone of many of the patients in the present study. There is macular choroidal thickening of 2 to 3 lm/mm Hg lowering of IOP. By contrast, our peripapillary measurements of choroidal thickness at the BMO showed minor and variable change compared with those of the macular zone.

Harry A. Quigley

Papers

High Efficiency Transfection of Rat Retinal Ganglion Cells by a Modified Adeno-associated Virus Incorporating the Woodchuck Hepatitis Post-transcriptional Regulatory Element

Structural engraftment and topographic spacing of transplanted human stem cell-derived retinal ganglion cells

CNTF Over-Expression Leads to Increased Retinal Ganglion Cell Survival in Experimental Glaucoma

Author Response: Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes.

Losartan is neuroprotective in experimental mouse glaucoma