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.

Violet and blue light blocking intraocular lenses: photoprotection versus photoreception.

AIM: To analyse how intraocular lens (IOL) chromophores affect retinal photoprotection and the sensitivity of scotopic vision, melanopsin photoreception, and melatonin suppression. METHODS: Transmittance spectra of IOLs, high pass spectral filters, human crystalline lenses, and sunglasses are used with spectral data for acute ultraviolet (UV)-blue photic retinopathy ("blue light hazard" phototoxicity), aphakic scotopic luminous efficiency, melanopsin sensitivity, and melatonin suppression to compute the effect of spectral filters on retinal photoprotection, scotopic sensitivity, and circadian photoentrainment. RESULTS: Retinal photoprotection increases and photoreception decreases as high pass filters progressively attenuate additional short wavelength light. Violet blocking IOLs reduce retinal exposure to UV (200-400 nm) radiation and violet (400-440 nm) light. Blue blocking IOLs attenuate blue (440-500 nm) and shorter wavelength optical radiation. Blue blocking IOLs theoretically provide better photoprotection but worse photoreception than conventional UV only blocking IOLs. Violet blocking IOLs offer similar UV-blue photoprotection but better scotopic and melanopsin photoreception than blue blocking IOLs. Sunglasses provide roughly 50% more UV-blue photoprotection than either violet or blue blocking IOLs. CONCLUSIONS: Action spectra for most retinal photosensitisers increase or peak in the violet part of the spectrum. Melanopsin, melatonin suppression, and rhodopsin sensitivities are all maximal in the blue part of the spectrum. Scotopic sensitivity and circadian photoentrainment decline with ageing. UV blocking IOLs provide older adults with the best possible rhodopsin and melanopsin sensitivity. Blue and violet blocking IOLs provide less photoprotection than middle aged crystalline lenses, which do not prevent age related macular degeneration (AMD). Thus, pseudophakes should wear sunglasses in bright environments if the unproved phototoxicity-AMD hypothesis is valid.

Micropulse and continuous wave diode retinal photocoagulation: visible and subvisible lesion parameters.

BACKGROUND/AIM: Subvisible micropulse diode laser photocoagulation localises retinal laser damage because brief micropulses allow little time for heat conduction to spread temperature rise from the retinal pigment epithelium to the neural retina. Treatment power is often chosen as a multiple of that needed for visible continuous wave lesions. The authors measured clinical laser powers needed for visible end point micropulse and continuous wave diode laser retinal photocoagulation. METHODS: Six parallel rows of 10 diode laser (810 nm) burns were made in the superior peripheral retina of six consecutive patients undergoing their initial frequency doubled Nd:YAG (532 nm) panretinal photocoagulation for proliferative or severe non-proliferative diabetic retinopathy. All photocoagulation exposures were 125 microm in retinal diameter and 0.2 seconds in duration. Micropulse exposures were performed with 500 Hz, 0.3 ms micropulses. The minimal power needed (1) for visible continuous wave diode photocoagulation was determined from two adjacent rows of laser lesions and (2) for visible micropulse diode photocoagulation from four additional adjacent rows of laser lesions. Fluorescein angiograms and red-free fundus photographs were obtained immediately and 6 days after laser photocoagulation in each patient. Calculations were performed to determine the extent to which clinical parameters exceeded ANSI Z136.1-2000 maximal permissible exposure (MPE) levels for laser exposure. RESULTS: Continuous wave and micropulse lesions typically required 300 mW (60 mJ) and 1800 mW (54 mJ), respectively. Visible continuous wave and micropulse lesions exceeded MPE levels by multiples of 36 x and 133 x, respectively. Laser energies were similar for visible continuous wave and micropulse lesions. CONCLUSION: Visible micropulse lesions require 6 x more power but roughly the same energy as visible continuous wave lesions. No significant difference was demonstrable in the minimal power needed for photographically and angiographically apparent diode micropulse lesions. MPE levels are designed to provide a 10 x safety margin. This safety margin was 3.7 x greater for micropulse than continuous wave diode laser photocoagulation.

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.

How much blue light should an IOL transmit?

Older, and even some modern, intraocular lenses (IOLs) transmit potentially hazardous ultraviolet radiation (UVR) to the retina. In addition, IOLs transmit more blue and green light to the retina for scotopic vision than the crystalline lenses they replace, light that is also potentially hazardous. The severity of UVR-blue type phototoxicity increases with decreasing wavelength, unlike the action spectrum of blue-green type retinal phototoxicity and the luminous efficiency of scotopic vision which both peak in the blue-green part of the optical spectrum around 500 nm. Theoretically, UVR+blue absorbing IOLs provide better retinal protection but worse scotopic sensitivity than UVR-only absorbing IOLs, but further study is needed to test this analysis. UVR is potentially hazardous and not useful for vision, so it is prudent to protect the retina from it with chromophores in IOLs. Determining authoritatively how much blue light an optimal IOL should block requires definitive studies to determine (1) the action spectrum of the retinal phototoxicity potentially involved in human retinal ageing, and (2) the amount of shorter wavelength blue light required for older adults to perform essential activities in dimly lit environments.

Why HID headlights bother older drivers.

Driving requires effective coordination of visual, motor, and cognitive skills. Visual skills are pushed to their limit at night by decreased illumination and by disabling glare from oncoming headlights. High intensity discharge (HID) headlamps project light farther down roads, improving their owner's driving safety by increasing the time available for reaction to potential problems. Glare is proportional to headlamp brightness, however, so increasing headlamp brightness also increases potential glare for oncoming drivers, particularly on curving two lane roads. This problem is worse for older drivers because of their increased intraocular light scattering, glare sensitivity, and photostress recovery time. An analysis of automobile headlights, intraocular stray light, glare, and night driving shows that brightness rather than blueness is the primary reason for the visual problems that HID headlights can cause for older drivers who confront them. The increased light projected by HID headlights is potentially valuable, but serious questions remain regarding how and where it should be projected.

Transpupillary thermotherapy for age-related macular degeneration: principles and techniques.

Transpupillary thermotherapy (TTT) is a subthreshold, low irradiance, long exposure duration, large spot size, infrared diode laser protocol. Retinal temperature increases in TTT for choroidal neovascularization (CNV) are substantially lower than those in conventional short-pulse photocoagulation, but they are maintained for 60 seconds to achieve therapeutic results. Treatment power is adjusted for retinal lesion size, chorioretinal pigmentation, macular elevation and media clarity. TTT uses 810-nm diode laser infrared radiation, which has no significant retinal phototoxicity. A parfocal laser delivery system is required to assure uniformity of irradiance across large diameter treatment spots. Relative contraindications for TTT include dense subretinal hemorrhage, prior focal photocoagulation and serous RPE detachment. Adverse events are rare, and include decreased vision and retinal arteriole occlusion. Randomized, prospective multi-center trials are underway to compare the results of TTT for occult CNV in age-related macular degeneration to the natural history of the disorder. Imaging, electrophysiologic or thermometric techniques may ultimately provide intra-operative or post-operative monitoring to assure the adequacy of TTT for CNV, despite the absence of ophthalmoscopically visible lesions.

Ophthalmoscopic contact lenses for transpupillary thermotherapy.

Ophthalmoscopic contact lenses for transpupillary thermotherapy (TTT) must provide effective visualization of retinal treatment sites and transmission of infrared diode laser radiation. Selection and proper use of retinal laser lenses requires knowledge of their lateral magnification, laser beam magnification factor, field of view and resolution. Optical performance is analyzed for Goldmann-type lenses and a series of inverted image lenses of differing magnification. Goldmann lenses have the highest resolution, but inverted image lenses of comparable magnification have 2.5 times or more their field of view. Inverted image lenses of similar magnification can differ in resolution. They require 2-4% more incident laser power to produce the same retinal irradiance as a Goldmann lens, but this difference is small in comparison to other clinical variables. Tilting an ophthalmoscopic contact lens up to 15 degrees causes little distortion in the circularity of the retinal spot formed by a laser beam or difference in retinal irradiance across the spot. Inverted image lenses produce higher anterior segment irradiances than Goldmann-type lenses, but anterior segment injuries are less likely in TTT than conventional visible light, short-pulse retinal photocoagulation because of the comparatively low irradiances used in TTT and the decreased absorption of diode laser infrared radiation in ocular media and melanin.

Transpupillary thermotherapy (TTT) of occult choroidal neovascularization: a retrospective, noncomparative case series of fifty-seven eyes.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of occult choroidal neovascularization. METHODS: A retrospective, noncomparative case series of 57 eyes of 52 patients who presented with occult subfoveal CNV and were treated with TTT. RESULTS: 83% of eyes were either stable (+/- one line) or showed improvement in visual acuity. 83% of eyes showed stabilization of their exudative process after one TTT treatment as evidenced by resorption of subretinal and/or intraretinal exudate or hemorrhage. Nine percent of eyes developed classic CNV during the mean follow-up time of ten months. CONCLUSIONS: TTT appears to stabilize the exudative process in eyes with occult CNV. A prospective, sham-controlled, randomized study (TTT4CNV Clinical Trial) is currently underway to directly compare TTT to the natural history of occult CNV.

Transpupillary thermotherapy for age-related macular degeneration: long-pulse photocoagulation, apoptosis, and heat shock proteins.

OBJECTIVE: To provide a biophysical foundation for using transpupillary thermotherapy (TTT) to manage choroidal neovascularization in age-related macular degeneration (ARMD). METHODS: Retinal temperature rise in laser therapy is proportional to retinal irradiance (laser power/area) for a particular spot size, exposure duration, and wavelength. TTT is a low irradiance, large spot size, prolonged exposure (long-pulse), infrared laser photocoagulation protocol. Results from an experimentally confirmed, finite element model of retinal light absorption and heat conduction are used to analyze laser parameter selection and its consequences. Results from apoptosis, heat shock protein and hyperthermia research are used to examine how chorioretinal damage from clinical procedures might be reduced. RESULTS: Chorioretinal thermal equilibration occurs during long-pulse TTT photocoagulation. Retinal temperature increases are similar in the RPE where laser radiation absorption is significant and in the adjacent neural retina where there is negligible radiation absorption. For parameters used to treat occult choroidal neovascularization in lightly-pigmented fundi (800-mW, 810-nm, 3-mm retinal spot diameter, 60-sec exposure duration), the maximum chorioretinal temperature elevation is calculated to be roughly 10 degrees C, significantly lower than the 20 degrees C temperature elevations measured in threshold, conventional short-pulse retinal photocoagulation. CONCLUSIONS: To achieve a preselected temperature rise, TTT laser power must be increased or decreased in proportion to the diameter rather than the area of the laser spot. Clinical power settings should be adjusted for fundus pigmentation and media clarity because both of these factors affect absorbed retinal irradiance and thus retinal temperature rise. Noninvasive thermal dosimetry currently is unavailable for clinical retinal photocoagulation, but potential thermometric techniques include MRI, liposomal-encapsulated dyes, multispectral imaging or reflectometry, and subretinal or episcleral thermometry. TTT may be useful not only as independent therapy, but also as an adjunct to PDT, antiangiogenic drugs and ionizing radiation therapy in the management of neovascular ARMD. Low temperature, long-pulse photocoagulation is a potential strategy for decreasing neural retinal damage in subsequent TTT or short-pulse photocoagulation and perhaps even for treating glaucoma or retinal degenerations.

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.

Free radical production by Nd:YAG laser photodisruption.

BACKGROUND AND OBJECTIVES: Plasma and cavitation bubble formation during optical breakdown in aqueous media may produce hydroxyl (*OH) radicals. The authors' objectives were to detect *OH produced by a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser photodisruptor and to determine *OH concentration in relation to laser energy. MATERIALS AND METHODS: *OH was assayed by measuring absorbance of triiodide (I3-) in a potassium iodide (KI) solution exposed to optical breakdown by an Nd:YAG laser. The concentration-dependent reduction of radical production in relation to cystamine concentration was evaluated. RESULTS: I3- concentration increased linearly with total irradiation energy and decreased exponentially with increasing cystamine concentration. *OH concentration was calculated using extinction coefficients of I3- and chemical equations relating I3- formation to *OH. CONCLUSIONS: The authors calculated that approximately 4 x 10(-12) moles of *OH are produced in a typical posterior capsulotomy of 100 mJ of total energy. This *OH concentration could produce strand breaks in approximately 0.4% of vitreous hyaluronic acid molecules, but is unlikely to produce clinical effects.