Martin A. Mainster

Circadian photoreception: ageing and the eye’s important role in systemic health

Aim: To analyse how age-related losses in crystalline lens transmittance and pupillary area affect circadian photoreception and compare the circadian performance of phakic and pseudophakic individuals of the same age. Methods: The spectral sensitivity of circadian photoreception peaks in the blue part of the spectrum at approximately 460 nm. Photosensitive retinal ganglion cells send unconscious information about environmental illumination to non-visual brain centres including the human body’s master biological clock in the suprachiasmatic nuclei. This information permits human physiology to be optimised and aligned with geophysical day–night cycles using neural and hormonal messengers including melatonin. Age-related transmittance spectra of crystalline lenses and photopic pupil diameter are used with the spectral sensitivity of melatonin suppression and the transmittance spectra of intraocular lenses (IOLs) to analyse how ageing and IOL chromophores affect circadian photoreception. Results: Ageing increases crystalline lens light absorption and decreases pupil area resulting in progressive loss of circadian photoreception. A 10-year-old child has circadian photoreception 10-fold greater than a 95-year-old phakic adult. A 45-year-old adult retains only half the circadian photoreception of early youth. Pseudophakia improves circadian photoreception at all ages, particularly with UV-only blocking IOLs which transmit blue wavelengths optimal for non-visual photoreception. Conclusions: Non-visual retinal ganglion photoreceptor responses to bright, properly timed light exposures help assure effective circadian photoentrainment and optimal diurnal physiological processes. Circadian photoreception can persist in visually blind individuals if retinal ganglion cell photoreceptors and their suprachiasmatic connections are intact. Retinal illumination decreases with ageing due to pupillary miosis and reduced crystalline lens light transmission especially of short wavelengths. Inadequate environmental light and/or ganglion photoreception can cause circadian disruption, increasing the risk of insomnia, depression, numerous systemic disorders and possibly early mortality. Artificial lighting is dimmer and less blue-weighted than natural daylight, contributing to age-related losses in unconscious circadian photoreception. Optimal intraocular lens design should consider the spectral requirements of both conscious and unconscious retinal photoreception.

Subthreshold diode micropulse photocoagulation for the treatment of clinically significant diabetic macular oedema

Aim: To report the visual and clinical outcomes of a pilot study of subthreshold diode micropulse (SDM) laser photocoagulation for clinically significant diabetic macular oedema (CSMO). Methods: The results of infrared (810 nm) SDM laser photocoagulation for CSMO were retrospectively reviewed in 95 eyes of 69 consecutive patients with mild to moderate non-proliferative diabetic retinopathy. The same laser parameters were used for each patient. Only the number of laser applications varied between patients, depending on their macular findings. Primary outcome measures were Snellen visual acuity, fluorescein angiographic leakage, and CSMO status. Results: Visual acuity was stable or improved in 85% of treated eyes, with a mean follow up of 12.2 months (range 3–29 months). CSMO decreased in 96% and resolved in 79% of treated eyes. No adverse laser events occurred. No laser lesions were detectable ophthalmoscopically or angiographically after treatment, consistent with calculations based on ANSI Z136.1 laser safety standards suggestive of only histologically detectable tissue effects at the laser exposure levels. No laser scarring was observed during the follow up period. Conclusion: Subthreshold diode micropulse laser photocoagulation minimises chorioretinal damage in the management of CSMO and demonstrates a beneficial effect on visual acuity and CSMO resolution. Prospective studies are needed to fully evaluate this technique.

The fractal properties of retinal vessels: Embryological and clinical implications

The branching patterns of retinal arterial and venous systems have characteristics of a fractal, a geometrical pattern whose parts resemble the whole. Fluorescein angiogram collages were digitised and analysed, demonstrating that retinal arterial and venous patterns have fractal dimensions of 1.63 ± 0.05 and 1.71 ± 0.07, respectively, consistent with the 1.68 ± 0.05 dimension of diffusion limited aggregation. This finding prompts speculation that factors controlling retinal angiogenesis may obey Laplaces equation, with fluctuations in the distribution of embryonic cell-free spaces providing the randomness needed for fractal behaviour and for the uniqueness of each individuals retinal vascular pattern. Since fractal dimensions characterise how completely vascular patterns span the retina, they can provide insight into the relationship between vascular patterns and retinal disease. Fractal geometry offers a more accurate description of ocular anatomy and pathology than classical geometry, and provides a new language for posing questions about the complex geometrical patterns that are seen in ophthalmic practice.

Decreasing Retinal Photocoagulation Damage: Principles and Techniques

Conventional suprathreshold retinal photocoagulation is a destructive procedure, but chorioretinal damage can be decreased by changing laser parameters and clinical endpoints. Laser effects can be localized by decreasing laser wavelength, spot size, and exposure duration, as well as by adopting threshold or subthreshold treatment protocols. Problems with short-pulse treatment regimens can be circumvented by the use of repetitively pulsed laser photocoagulators. Preliminary clinical results with reduced-damage photocoagulation methods are promising and await confirmation in larger, controlled clinical trials.

Wavelength Selection in Macular Photocoagulation: Tissue Optics, Thermal Effects, and Laser Systems

The therapeutic effects of macular photocoagulation result from focal heating of the retina and choroid. The magnitude, spatial extent, and duration of temperature increases produced by laser exposures are influenced by light scattering in intraocular and intraretinal transit; light absorption by melanin, hemoglobin, and xanthophyll in target tissues; and beam parameters, such as wavelength, spot size, and exposure duration. Tissue optics and thermodynamics provide a useful guide for selecting new laser systems of potential value in macular photocoagulation, but laser-tissue interactions and subsequent chorioretinal responses are poorly understood, and therapeutic efficacy can be established only by controlled clinical trials.

The role of environmental light in sleep and health: Effects of ocular aging and cataract surgery.

Environmental illumination profoundly influences human health and well-being. Recently discovered photoreceptive retinal ganglion cells (pRGCs) are primary mediators of numerous circadian, neuroendocrine and neurobehavioral responses. pRGCs provide lighting information to diverse nonvisual (non-image-forming) brain centers including the suprachiasmatic nuclei (SCN) which serve as the bodys master biological clock. The SCN exert functional control over circadian aspects of physiology. The timing and strength (amplitude) of SCN rhythmic signals are affected by light exposure. Light deficiency may attenuate SCN function and its control of physiological and hormonal rhythms which in turn can result in a cascade of adverse events. Inadequate pRGC photoreception cannot be perceived consciously, but may aggravate many common age-associated problems including insomnia, depression and impaired cognition. In this review we (1) summarize circadian physiology, emphasizing lights critical role as the most important geophysical timing cue in humans; (2) analyze evidence that typical residential lighting is insufficient for optimal pRGC requirements in youth and even more so with advancing age; (3) show how ocular aging and cataract surgery impact circadian photoreception; and (4) review some of the diverse morbidities associated with chronodisruption in general and those which may be caused by light deficiency in particular.

Light and macular degeneration: A biophysical and clinical perspective

The evidence linking photic retinopathy to ageing macular degeneration (AMD) is compelling but circumstantial. The biophysical foundations of ageing theory are presented, in addition to an analysis of retinal senescence and the potential contributory role of photochemical retinal damage. Although there is pressure to implement clinical therapy for AMD based on laboratory studies of photic retinopathy, there is no evidence at this time that any such therapy is effective. Nonetheless, until the relationship between photic retinopathy and AMD is better understood, it is appropriate for individuals to use ultraviolet and deep blue protective sunglasses in bright environments, particularly if they have reduced ocular pigmentation or if they are aphakes or pseudophakes without an ultraviolet-protective intraocular lens.

The Spectra, Classification, and Rationale of Ultraviolet-Protective Intraocular Lenses

I measured the spectral transmittance of 16 implantable intraocular lenses from 12 manufacturers and examined the rationale for using ultraviolet-absorptive intraocular lenses to protect pseudophakic individuals from photic retinopathy. Each ultraviolet-protective lens was classified by the wavelength at which its spectral transmittance fell to 10% in the blue or ultraviolet region of the spectrum. Current ultraviolet-protective intraocular lenses differ in the effectiveness of their protection against photic retinopathy, and product descriptions may be misleading.

The effect of chromatic dispersion on pseudophakic optical performance.

Aim: Monochromatic and chromatic aberrations limit the visual performance of pseudophakic eyes. Chromatic aberration is caused by the chromatic dispersion of optical materials which can be characterised by their Abbe numbers. This study examines how chromatic dispersion affects pseudophakic optical performance at different wavelengths and spatial frequencies. Methods: Abbe numbers were measured for acrylic and silicone intraocular lenses (IOLs). A schematic eye model based on cataract population data was used to compute monochromatic and photopic polychromatic modulation transfer functions (MTFs) for pseudophakic eyes with aspheric IOLs. IOL Abbe numbers were varied without changing other eye model parameters to determine how chromatic dispersion affects pseudophakic MTF and chromatic difference of refraction. Additional calculations were performed for (1) acrylic or silicone materials and (2) high-pass optical filters blocking either UV radiation or UV radiation and short wavelength visible light. Results: Shorter wavelengths account for approximately two thirds of pseudophakic chromatic difference of refraction or longitudinal chromatic aberration. Increasing Abbe number (reducing chromatic dispersion) decreases total chromatic difference of refraction and increases photopic polychromatic MTF. For a specific spatial frequency, there is an effective pseudophakic depth of wavelength over which a particular MTF level is achieved or exceeded. Depth of wavelength narrows with decreasing Abbe number or increasing spatial frequency. Blue-blocking IOL chromophores improve photopic MTF performance by less than 1.5%. Conclusions: Most pseudophakic longitudinal chromatic aberration arises from the chromatic dispersion of IOLs rather than the cornea and other ocular media. Increasing the Abbe number of optic materials improves overall pseudophakic optical performance. Optical transmission of medium and high spatial frequency modulation information has a spectrum similar to photopic luminous efficiency, accounting for the inability of blue-blocking chromophores to improve photopic pseudophakic contrast sensitivity significantly and demonstrating the excellent mutual adaptation of modulation transfer by the eye’s optics and management of that data by the retina and brain.

Glare's Causes, Consequences, and Clinical Challenges After a Century of Ophthalmic Study

PURPOSE To provide a multidisciplinary synthesis of scientific information on disability, discomfort, dazzling, and scotomatic (photostress) glare. DESIGN Perspective. METHODS Analysis and integration of relevant historical and contemporary publications on glare in ophthalmology, illumination engineering, neurology, and other relevant disciplines. RESULTS Disability glare is caused by scattered intraocular light (straylight) not useful for vision. Straylight casts a veiling luminance on the retina, reducing image contrast and impairing vision. In common environments, glare and target illumination sources have the same or similar spectra. Colored spectacle or intraocular lens filters reduce both proportionately, so they do not increase retinal image contrast or decrease disability glare. Discomfort glare is caused by situational illumination too intense or variable. Dazzling glare occurs when high illuminances are spread across the retina. Neurophysiological research is clarifying how discomfort and dazzling glare depend on different retinal photoreceptors and nociceptive brain pathways involving the trigeminal ganglion and thalamus. Photostress is caused by excessive local retinal photopigment bleaching uncommon in ordinary situations. Optical glare countermeasures are available for daytime driving but not oncoming automobile headlights at night. Filters that decrease daytime discomfort or dazzling glare also reduce nighttime mesopic and scotopic sensitivity. CONCLUSIONS Glare is problematic for patients and clinicians despite a century of scientific research. Advances in understanding glare have been hampered by its complex, multidisciplinary nature and limited interdisciplinary communication. We provide one pathway through the forest of glare nomenclature and mechanisms. Improved diagnostic and therapeutic methodologies await continuing progress in understanding glare.