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Importance: Solar retinopathy is a rare form of retinal injury that occurs after direct sungazing., Objective: To enhance understanding of the structural changes that occur in solar retinopathy by obtaining high-resolution in vivo en face images., Design, Setting, and Participant: Case report of a young adult woman who presented to the New York Eye and Ear Infirmary with symptoms of acute solar retinopathy after viewing the solar eclipse on August 21, 2017., Main Outcomes and Measures: Results of comprehensive ophthalmic examination and images obtained by fundus photography, microperimetry, spectral-domain optical coherence tomography (OCT), adaptive optics scanning light ophthalmoscopy, OCT angiography, and en face OCT., Results: The patient was examined after viewing the solar eclipse. Visual acuity was 20/20 OD and 20/25 OS. The patient was left-eye dominant. Spectral-domain OCT images were consistent with mild and severe acute solar retinopathy in the right and left eye, respectively. Microperimetry was normal in the right eye but showed paracentral decreased retinal sensitivity in the left eye with a central absolute scotoma. Adaptive optics images of the right eye showed a small region of nonwaveguiding photoreceptors, while images of the left eye showed a large area of abnormal and nonwaveguiding photoreceptors. Optical coherence tomography angiography images were normal in both eyes. En face OCT images of the right eye showed a small circular hyperreflective area, with central hyporeflectivity in the outer retina of the right eye. The left eye showed a hyperreflective lesion that intensified in area from inner to middle retina and became mostly hyporeflective in the outer retina. The shape of the lesion on adaptive optics and en face OCT images of the left eye corresponded to the shape of the scotoma drawn by the patient on Amsler grid., Conclusions and Relevance: Acute solar retinopathy can present with foveal cone photoreceptor mosaic disturbances on adaptive optics scanning light ophthalmoscopy imaging. Corresponding reflectivity changes can be seen on en face OCT, especially in the middle and outer retina. Young adults may be especially vulnerable and need to be better informed of the risks of viewing the sun with inadequate protective eyewear.

Blunt ocular trauma from a child's plastic foam-covered toy baseball bat caused traumatic optic neuropathy and choroidal rupture in a 9-year-old child. The examination revealed a visual acuity of 6/60, a relative afferent pupillary defect, optic nerve swelling, commotio retinae and retinal haemorrhages. There was no orbital fracture or intraorbital haematoma on CT scanning. Optical coherence tomography showed macular oedema and disruption of the retinal pigment epithelium and Bruch's membrane. The child was admitted for intravenous methylprednisolone and discharged on topical steroid treatment. At 1 month follow-up, visual acuity had improved to 6/12. Optic nerve swelling had resolved and the fundus had two crescent-shaped choroidal rupture scars. Choroidal rupture and optic neuropathy can be secondary to indirect trauma, and even when the mechanism of injury is with a piece of equipment designated as suitable for children, serious ocular injury can occur.

Purpose: To examine the inner surface of the sclerotomy during microincision vitrectomy surgery by Miyake-Apple view., Methods: The anterior half of porcine eyes was attached to a transparent acrylic plate with cyanoacrylate glue. Then, either a 23-gauge or a 25-gauge trocar-cannula was inserted through the sclera obliquely. The inner surface of the entrance site was observed posteriorly by Miyake-Apple view. These images were compared with the endoscopic view of two patients who underwent vitreous surgery for an epiretinal membrane., Results: When the trocar-cannula was inserted obliquely, the Miyake-Apple view showed that the ciliary epithelium at the sclerotomy site was stretched. When the trocar-cannula was inserted vertically, the ciliary epithelium was folded, and the folds remained even after the trocar was removed. Vitreous strands were seen incarcerated into the sclerotomy site. In human eyes, a folding of the ciliary epithelium was not clearly seen with the endoscopic view but the incarcerated vitreous was seen., Conclusion: The Miyake-Apple view provided a precise, in vivo, observation of the inner surface of the entry site. It disclosed the morphological stress on the ciliary epithelium by the sclerotomy., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Aim: To investigate whether retinal pigment epithelium (RPE)-choroid translocation would be a suitable treatment for RPE tears, which have a poor prognosis and are encountered more often since the introduction of anti-(vascular endothelial growth factor (VEGF)) therapy for exudative age-related macular degeneration (AMD)., Methods: Prospective interventional case series of six eyes of six patients with AMD with an RPE tear treated with an RPE-choroid translocation. The RPE tear occurred in a vascularised pigment epithelium detachment in four patients and after treatment in the other two. Preoperative and postoperative evaluation included ETDRS visual acuity (VA) and fixation testing. The follow-up period ranged from 6 months to 2 years., Results: The mean preoperative VA was 20/160 (range 20/400-20/80). The mean VA at the last examination after surgery was 20/80 (range 1/60-20/50). One of the six patients had a preoperative VA of >/=20/80, and four had a VA of 20/80 or better at their last examination. Foveal fixation on the graft was present in five of the six eyes up to the last examination., Conclusion: These preliminary data show that an RPE-choroid translocation may be a treatment option for patients with an RPE tear.

Background: It has been shown that selective retina treatment (SRT) using a train of 1.7 microseconds laser pulses allows selective damage of the retinal pigment epithelium (RPE) while sparing the adjacent photoreceptors and thus avoiding laser scotoma. It was the purpose of this work to investigate SRT laser effects with Q-switched pulses of only 8 nanoseconds in duration by evaluating the angiographic and ophthalmoscopic damage thresholds and the damage range by histology in a rabbit model., Materials and Methods: A flash lamp pumped frequency doubled (532 nm) Nd:YAG laser with 8 nanoseconds pulse duration was used. In total 210 laser lesions, each calculated to be 102 microm in diameter on retina, were applied through a slit lamp onto the fundus of six eyes of Chinchilla Bastard rabbits. The rabbits were irradiated with increasing energies with single pulses and a train of 10 laser pulses at 10 Hz. After treatment fundus photography and angiography were performed to determine the damage thresholds (ED(50)-probability of RPE cell damage and neurosensory retinal damage) as well as the safety range between both thresholds (ratio of angiographic ED(86) vs. ophthalmoscopic ED(14)). Selected histology was taken for single and repetitive pulse lesions after treatment., Results: Angiographic and ophthalmoscopic ED(50)-thresholds decreased with increasing number of pulses. For single pulse application ophthalmoscopic and angiographic ED(50) were determined to 365 and 144 mJ/cm(2), respectively. Regarding 10 pulses 266 and 72 mJ/cm(2) were found. No retinal hemorrhages or disruptions were observed for both sets of parameters. The therapeutic window between angiographic and ophthalmoscopic threshold revealed a factor of 3.1 for single pulses and 2.3 for repetitive pulse irradiation. The safety range respectively had a factor of 0.8 (single pulses) and 1.7 (10 pulses). Histologic examination of laser lesions with single and repetitive pulses at radiant exposures within the therapeutic window-292 and 213 mJ/cm(2) respectively-revealed damaged RPE, intact Bruch's membrane and choriocapillaries. Photoreceptors were partly spared but also damaged to various extents., Conclusions: Short laser pulses of 8 nanoseconds pulse duration can damage the RPE without retinal hemorrhage or disruption. Selective damage of the RPE without affecting the photoreceptors can only rarely be achieved due to the small safety range. Thus, so far microsecond laser pulses for SRT seems favorable compared to nanosecond pulses in order to prevent unintentional photoreceptor damage.

Purpose: To detect retinal pigment epithelium (RPE) tears in predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with intravitreal bevacizumab injections., Methods: Forty consecutive patients with predominantly classic CNV secondary to AMD were treated with 1.25 mg of intravitreal bevacizumab. Patients were evaluated with visual acuity (VA) measured with Early Treatment Diabetic Retinopathy Study charts, optical coherence tomography, and fluorescein angiography., Results: Three patients developed a RPE tear after the first injection. The first patient had been treated with verteporfin therapy and VA remained unchanged. In the other two cases the CNV was naive and VA improved since the foveal center was not involved by the tear and macular edema was reduced., Conclusions: RPE tears can occur following intravitreal bevacizumab injections in patients with predominantly classic CNV although VA is not always affected.

Purpose: Selective targeting of the retinal pigment epithelium (RPE) with repetitive laser pulses that minimize thermal damage to the adjacent photoreceptors is a promising new therapeutic modality for RPE-related retinal diseases. The selectivity of an alternative, more versatile scanning approach was examined in vivo by using a broad range of scanning parameters., Methods: Acousto-optic deflectors repeatedly scanned the focus of a continuous wave (cw)-laser across the retina of Dutch belted rabbits, producing microsecond irradiation at each RPE cell. Two irradiation patterns forming separated lines (SEP) or interlaced lines (INT), different dwell times (2.5-75 micros), and repetition numbers (10 and 100 scans with 100-Hz repetition rate) were tested. Thresholds were evaluated by fundus imaging and angiography. Histology was performed for selected parameters., Results: Selective RPE cell damage was obtained with moderate laser power. The angiographic threshold power decreased with pulse duration, number of exposures, and applying the INT pattern. Ophthalmoscopic thresholds, indicating onset of thermal coagulation, were higher than twice the angiographic threshold for most tested parameters. Histology confirmed selective RPE cell damage for SEP irradiation with 7.5 and 15 micros; slower scan speeds or closed lines caused photoreceptor damage., Conclusions: A cw-laser scanner can be set up as a highly compact and versatile device. Selective RPE damage is feasible with dwell times up to 15 micros. Greatest selectivity is achieved with short exposure times and separated scan lines. Interlaced lines and long exposure times facilitate heat conduction into photoreceptors. A scanner is an attractive alternative for pulsed selective targeting, because both selective targeting and thermal photocoagulation can be realized.

Solar maculopathy is caused by sun-gazing without protection and in most cases appears to be reversible. Retinal damage may be caused by photochemical changes combined with a rise in temperature at the time of sun observation. We report a case of bilateral solar retinopathy following direct sun gazing after observation of the partial eclipse on 3 October 2005. A 25-year-old Caucasian man presented 24 h after watching the eclipse with symptoms of blurred vision and a bright positive central scotoma. Total direct viewing time was approximately 5 min. While observing the eclipse, the patient kept both eyes open. On presentation, his visual acuity was 20/25 in his right eye and 20/32 in his left eye. Ophthalmoscopic examination revealed a bilateral yellowish-white spot in the center of the foveal region. Static visual field examination did not disclose any absolute scotoma but a decrease in the foveal threshold was noted in both eyes. Optical coherence tomography (OCT) examination revealed a bilateral increased reflectivity of the inner foveal retina that was greater in the left eye. This finding was associated with a hyporeflective area of the underlying retinal pigment epithelium: choriocapillaris complex and an increase in retinal thickness. Eight days later, visual acuity was 20/20 in each eye. Funduscopy showed the yellow lesion had vanished. Four months after exposure, funduscopy was normal and OCT scan showed normal reflectivity of all retinal layers in the fovea. However, static visual field examination disclosed a decreased foveal threshold on the left eye. We compare the OCT findings in this patient with the data reported in the literature. Indeed, various OCT findings have been reported depending on the intensity and frequency of sun exposure. This observation demonstrates that OCT appears to be potentially useful in the evolutive follow-up of solar maculopathy, and emphasizes the importance of eye safety during solar eclipse observation.

The computer modeling was applied for investigation of the processes of laser-induced tissue damage. The melanin granule models for the processes of laser-induced thermal damage and the results of computer modeling of the optical, thermophysical, and thermochemical processes during selective laser interaction with melanoprotein granules (melanosomes) in retinal pigment epithelium are presented in this paper. Physical-mathematical model and system of equations are formulated which describe thermal interaction processes for "short" laser pulses of duration t (p)<10(-6) s and for " long' pulses of duration t(p) > 10(-6) s. Results of numerical simulation of the processes give the space-time distributions of temperature and degrees of thermodenaturation of the protein molecules inside and around melanosomes and in the volume of irradiated tissues. Energy absorption, heat transfer and thermochemical (thermodenaturation, coagulation) processes occurring during the interaction of laser pulses with pigmented spherical and spheroidal granules in heterogeneous tissues are theoretically investigated. The possibility for selective interaction of short laser pulses with pigmented granules is discussed which results in the formation of denaturation microregions inside and near the pigmented granules (granular thermodenaturation) without origination of a continuous macroscopic thermodenaturation lesion in tissue. Analytical model of heating of single spherical and spheroidal granule under laser pulse is presented. Simple equations for time dependencies of particle temperature are obtained. The presented results are of essential interest for laser applications in and can be used for investigation of laser interaction with pigmented tissues in different fields of laser medicine.

Purpose: To correlate changes in primate fundus after transpupillary thermotherapy (TTT) at two wavelengths., Methods: Twelve primate eyes were treated with TTT using a wavelength of 635 nm (n=7) or 810 nm (n=5). Laser parameters were as follows: 635 nm (spot size, 1 mm; duration, 30-8 seconds; and fluence [power over time], 20-91.4 J/cm) and 810 nm (spot size, 2 mm; duration, 60 seconds; and fluence, 96-436 J/cm). Fundus photography, fluorescein and indocyanine green angiography, and enucleation were performed at time 0 or 2 weeks after TTT for histologic analysis., Results: Threshold for fundus lesions (91.4 J/cm at 635 nm and 191 J/cm at 810 nm), acute and chronic retinal damage shown by histologic analysis (79.2 J/cm at 635 nm and 96 J/cm at 810 nm), and choroidal vessel occlusion (50 J/cm at 635 nm and 96 J/cm at 810 nm) were lower at 635 nm. Disorganization of the retina and retinal pigment epithelium was seen for both wavelengths at time 0 and 2 weeks after TTT. Occlusion of the choriocapillaris and choroidal stromal vessels was noted only in specimens obtained 2 weeks after TTT., Conclusions: TTT resulted in acute and delayed damage to the neurosensory retina that persisted at 2 weeks. The 635-nm wavelength demonstrated a lower threshold fluence for visible fundus lesions, retinal damage, and choroidal vascular occlusion than the 810-nm laser.

Purpose: To describe retinal pigment epithelial tear following photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD)., Design: Retrospective interventional case series., Methods: A retrospective study in an institutional practice. We describe seven cases of retinal pigment epithelial (RPE) tear, which developed in seven eyes of seven patients following PDT. All eyes had subfoveal CNV secondary to AMD., Results: Six eyes had occult subfoveal CNV, and one eye had recurrent classic subfoveal CNV. In five patients, the eye that developed the tear was the second eye, whereas the first eye had a disciform scar. In four eyes, the RPE tear developed after one PDT, in one eye the RPE tear developed after the second PDT, and in two eyes the RPE tear developed after the third PDT. In five of seven cases, there was a significant visual deterioration following the RPE tear., Conclusions: RPE tear is a complication that may occur following PDT in particular when the PDT is applied to an occult subfoveal CNV.

Purpose: To investigate the cellular mechanisms involved in the cell death of human retinal pigment epithelial (hRPE) cells after their exposure to laser injury., Methods: Cultured human hRPE cells were irradiated for different lengths of time and at different levels of energy using diode laser photocoagulation coupled with an intraocular laser probe. Apoptosis was determined by TUNEL staining and annexin-V labeling of phosphatidylserine exposure. Ceramide levels were quantified by the diacylglycerol kinase assay using thin-layer chromatography., Results: Laser irradiation caused areas of apoptosis in the hRPE cells. These areas were detected around the ablated and necrotic laser scar and developed several hours after the laser irradiation. Laser irradiation concomitantly induced an increase in the intracellular production of ceramide, a lipid second messenger., Conclusions: The results demonstrate that laser irradiation induces apoptosis in hRPE cells and suggest that the underlying signaling mechanism involves ceramide generation.

Purpose: The retinal pigment epithelium (RPE) cells with their strongly absorbant melanosomes form the highest light-absorbing layer of the retina. It is well known that laser-induced retinal damage is caused by thermal denaturation at pulse durations longer than milliseconds and by microbubble formation around the melanosomes at pulses shorter than microseconds. The purpose of this work was to determine the pulse width when both effects merge. Therefore, the RPE damage threshold and mechanism of the damage at single laser pulses of 5-micros to 3-ms duration were investigated., Methods: An argon laser beam (lambda 514 nm) was externally switched by an acousto-optic modulator to achieve pulses with constant power in the time range of 5 micros up to 3 ms. The pulses were applied to freshly prepared porcine RPE samples serving as a model system. After laser exposure RPE cell damage was proved by the cell-viability stain calceinAM. Microbubble formation was detected by acoustic techniques and by reflectometry., Results: At a pulse duration of 5 micros, RPE cell damage was always associated with microbubble formation. At pulses of 50 micros, mostly thermal denaturation, but also microbubble formation, was detected. At the longer laser pulses (500 micros, 3 ms), RPE cell damage occurred without any microbubble appearance., Conclusions: At threshold irradiance, the transition time from thermal denaturation to thermomechanical damage of RPE cells is slightly below the laser pulse duration of 50 micros.

Background and Objectives: The therapeutic effect of laser treatment for macular diseases is related to the damage to the retinal pigment epithelium (RPE) and the subsequent restoration of the defect due to RPE proliferation. In contrast to conventional laser treatment, it is possible to damage the RPE selectively and to spare the photoreceptors by using repetitive microsecond laser pulses. It was the aim of the study to investigate the influence of pulse duration and number of pulses on angiographically and ophthalmoscopically visible retinal damage thresholds in order to optimize treatment modalities., Study Design/materials and Methods: In total, 625 laser lesions with various parameters were applied to the retina in 11 eyes of 6 Chinchilla breed rabbits using an experimental laser system (Nd:YLF at 527 nm). Pulse duration (1.7 microseconds and 200 nanoseconds) and number of pulses (100, 10, and 1 pulses) were varied at a constant repetition rate of 100 Hz. Damage thresholds were determined in terms of ophthalmoscopic and fluorescein angiographic visibility, and the therapeutic window (TW; angiographic ED(50) vs. ophthalmoscopic ED(50)) as well as the safety range (SR; angiographic ED(84) vs. ophthalmoscopic ED(16)) between both thresholds were calculated. Selected laser lesions were evaluated by histology., Results: Generally, the ED(50) radiant exposure for angiographic visibility decreases for shorter laser pulses and with an increase in the number of pulses. The TW for both pulse durations (1.7 microseconds and 200 nanoseconds) was wider with 100 pulses than with single pulses. The widest TW was found for 100 pulses at 200 nanoseconds pulse duration (5.9-fold above the angiographic threshold), and the smallest TW with a factor of 1.6 was found for 1.7 microseconds single pulses. In terms of SR, only irradiation with 100 pulses at 200 nanoseconds pulse duration was associated with a ratio >2. Independently of pulse duration, histological examination of laser sites 1 hour after irradiation revealed widely intact photoreceptors, while the underlying RPE was damaged., Conclusions: Pulse duration and number of pulses have a significant influence on RPE damage thresholds and consecutively on TW and SR. Because fundus pigmentation in humans may vary intra- and interindividually by a factor of 2, a large TW and ideally also a large SR should be ensured in a clinical treatment context. In rabbits, the safety range with 200 nanoseconds pulses is higher than with the pulse duration of 1.7 microseconds currently in clinical use. These findings suggest the need for clinical pilot studies to prove whether these results can be transposed to the situation in humans., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: To report traumatic, hemorrhagic detachment of the retinal pigment epithelium that was detected by optical coherence tomography., Design: Observational case report., Methods: A 17-year-old boy with hemorrhagic fundus lesions caused by blunt ocular trauma was examined by optical coherence tomography and angiography., Results: Initially, two dark red, mounded lesions were seen, with one in the macula and the other adjacent to the optic disk. The lesions blocked the fluorescence on fluorescein and indocyanine green angiography. Optical coherence tomography demonstrated dome-shaped elevations of the retinal pigment epithelium at each lesion. Four months later, the retinal pigment epithelium detachments disappeared in the tomography images, and no scarring was evident ophthalmoscopically. Small choroidal ruptures were detected in each lesion by angiography., Conclusions: Optical coherence tomography was useful in evaluating the site of the hemorrhage in the chorioretinal layers caused by blunt ocular trauma.

Purpose: To compare retinal pigment epithelium (RPE) resurfacing on the RPE basement membrane and inner collagenous layer (ICL) in human submacular Bruch's membrane explants., Methods: Debridements were created in RPE-choroid-sclera explants (mean donor age 71.91 +/- 7.76 years) to create defects exposing the RPE basement membrane (RPEbm(+) defects), the ICL immediately below the RPE basement membrane (superficial ICL, [SICL]) or deeper layers of the ICL (DICL). Eleven pairs of eyes--four pairs with one eye having an RPEbm(+) defect and the fellow eye having an SICL defect and seven pairs with corresponding RPEbm(+) and DICL defects--were observed for 10 days by visualizing RPE ingrowth with 4',6'-diamino-2-phenylindole (DAPI) filters. At day 10, specimens were processed for scanning electron microscopy., Results: Resurfacing of localized RPE defects occurred to some degree in all 11 pairs of eyes. No significant difference in the percentage of resurfacing of RPEbm(+) defects (67.35% +/- 18.82%) and SICL defects (64.26% +/- 16.07%) was observed although healing of the SICL showed more variability in the morphology of RPE cells migrating into the defect. Significant differences in healing were observed between pairs with RPEbm(+) defects versus DICL defects (84.07% +/- 15.35% and 54.00% +/- 14.54% resurfacing, respectively). RPE ingrowth into DICL defects exhibited the greatest morphologic variability., Conclusions: RPE basement membrane supports RPE resurfacing of localized RPE defects. The deeper portion of the ICL of aged submacular human Bruch's membrane does not support RPE resurfacing to the same extent as does the RPE basement membrane. The poor RPE resurfacing observed in DICL defects mimics the histopathological findings in patients with age-related macular degeneration after excision of choroidal new vessels.

Background and Objectives: Selective treatment of the retinal pigment epithelium (RPE) by repetitively applying green micros-laser pulses is a new method for retinal diseases associated with a degradation of the RPE, which spares the neural retina. We investigated an alternative approach to realize repetitive micros-laser exposure by rapidly scanning a continuous wave (CW)-laser beam across the RPE., Study Design/materials and Methods: An Ar(+) laser beam (514 nm) with a diameter of 18.75 microm was repetitively scanned across porcine RPE samples in vitro providing an irradiation time of 1.6 micros per point on the central scan axis. RPE cell damage was investigated by means of the fluorescence viability assay Calcein-AM., Results: The ED(50) cell damage is 305 mJ/cm(2) when applying 10 scans with a repetition rate of 500 Hz. The threshold decreases with the number of scans, a saturation was found at 135 mJ/cm(2) with more than 500 exposures applied. The depth of focus in beam direction is 350 microm, defined by an increase of the threshold radiant exposure by 20%., Conclusions: Targeting of pigmented cells with high local resolution has been proved with a laser-scanning device. Looking ahead selective RPE-treatment, the adaptation of a laser-scanning device on a slit-lamp or into a modified retina angiograph seems to be an attractive alternative to the pulsed micros laser device., (Copyright 2003 Wiley-Liss, Inc.)

Age-related macular degeneration and other eye diseases, such as diabetic retinopathy, are probably linked to the effects of oxygen radicals derived from light or metabolic reactions. We have investigated the effects of hypoxia on bovine retinal pigmented epithelial cells (RPE) and the response of these cells to two antioxidants that have previously shown a beneficial action against free radical-linked senescent involution. The main results of the study were as follows: (i) Hypoxia induced apoptotic damage on RPE cells, with LDH leakage and ATP reduction; (ii) both vitamin C (VC) and N-acetyl-cysteine (NAC) treatment protected against hypoxia-induced apoptosis, with less DNA fragmentation. In our opinion, these findings justify further experimental and clinical work to investigate the role of hypoxia in the mechanisms of age-related RPE injury and death as well as the potential of antioxidant administration to prevent or delay retinal degenerative processes caused by oxygen-dependent pathophysiological conditions., (Copyright 2002 S. Karger AG, Basel)

Background and Objective: In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities., Materials and Methods: Chinchilla-breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd:YLF laser (wave-length: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 micros, 1.7 micros, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 micros and 200 ms). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 microm (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile., Results: Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 microJ (5 micros), 32 microJ (1.7 micros), and 30 microJ (200 ns). The angiographic ED50 thresholds were 13.4 microJ (5 micros), 9.2 microJ (1.7 micros), and 6.7 microJ (200 ns). With the argon laser, the angiographic threshold for 5 micros pulses was 5.5 microJ. The ophthalmoscopic threshold could not be determined because of a lack of power; however, it was > 12 microJ. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd:YLF and 3.180 for the argon laser. Thus, the maximal ED50 -threshold radiant exposures for the Nd:YLF were calculated to be 362 mJ/cM2 (5 micros), 478 mJ/cm2 (1.7 micros), and 438 mJ/cm2 (200 ns) ophthalmoscopically. Angiographically, the thresholds were 189 mJ/cm2 (5 micros), 143 mJ/cm2 (1.7 micros), and 97 mJ/cm2 (200 ns). For the argon laser, the maximal ED50 radiant exposure threshold was 170 mJ/cm2 angiographically., Conclusion: The gap between the angiographic and the ophthalmoscopic thresholds for the 200 ns regime (4.5 times above angiographic ED50) was wider than for the 1.7 micros regime (3.3 times above the angiographic ED50). This would suggest the appropriate treatment would be 200 ns pulses. However, histologies have yet to prove that nonvisible mechanical effects increase with shorter pulse durations and could reduce the "therapeutic window." When comparing the thresholds with 5 micros pulses from the argon and Nd:YLF laser, it demonstrates that intensity modulations in the beam profile must be considered.

Background: The purpose of this study was to identify the profile of gene expression during retinal pigment epithelial (RPE) wound repair., Methods: ARPE-19 cells derived from a human RPE cell line were grown for 4 weeks and injured by creating multiple concentric wounds. Unwounded cultures served as controls. During the proliferative phase of wound repair, total RNA was extracted from control and wounded cultures, and a [32P]dATP-labeled cDNA probe was synthesized and hybridized to Atlas Arrays (Clontech, Palo Alto, Calif.) containing 588 cDNAs. The autoradiograms obtained were then analyzed using the Molecular Dynamics software program. Semiquantitative PCR was carried out to confirm up-regulation of four genes associated with wound repair. ELISA was performed to quantitate the secreted MCP-1., Results: In wounded cultures prominent up-regulation (greater than fivefold) was seen for genes encoding DNA synthesis and DNA repair proteins. A greater than threefold increase was seen for genes encoding mitogen-activated protein kinase, CD44, MCP-1 (monocyte chemotactic protein), thymosin beta-10, and HDGF (hepatoma-derived growth factor), among others. Genes encoding tumor suppressors were downregulated three- to five-fold in the wounded compared with the unwounded cultures. Semiquantitative PCR confirmed up-regulation of transcripts for thymosin beta-10, HDGF, CD44, and MCP-1. ELISA showed a 20% increase in secreted MCP-1., Conclusions: Gene array analysis revealed a differentiation program that included increased expression of genes involved in wound repair (adhesion molecules, cytokines, signal transducers), along with increased MCP-1 secretion. The RPE may be an early participant in the inflammatory response that occurs with proliferative vitreoretinopathy.

Objective: To examine the histologic, histochemical, and ultrastructural changes in Bruch membrane in mice on a high-fat diet with and without laser photochemical injury., Methods: Five groups of C57BL/6 mice were studied. Group 1 included 2-month-old mice on a normal diet; group 2 included 8-month-old mice on a normal diet; group 3 included 8-month-old mice on a high-fat diet; groups 4 and 5 included 8-month-old mice on a normal diet or high-fat diet, respectively, that underwent laser application of one eye with argon blue laser (488 nm). The mice were killed and plasma lipid levels were measured. The eyes were examined by standard electron microscopy, filipin histochemistry for unesterified cholesterol (UC) and esterified cholesterol (EC), and the osmium-tannic acid-phenylenediamine method for preserving extracellular lipid particles., Results: The plasma cholesterol level was significantly higher in the mice on the high-fat diet than the controls (P<.001). Bruch membrane was thicker in group 2 than group 1 (P =.04) and group 3 had a thicker Bruch membrane than group 2 (P =.003). All eyes in group 3 exhibited accumulation of electron-lucent debris. There was no histochemical and ultrastructural evidence that this material represented accumulated UC or EC. Seven of 9 laser-injured eyes in group 5 accumulated basal laminar deposit (BlamD)-like material in Bruch membrane (P =.02)., Conclusions: Electron-lucent debris accumulates in murine Bruch membrane, and the amount correlates with age and high-fat diet. This debris has some similarities with basal linear deposits, although the debris does not form a discrete layer external to the basement membrane of the retinal pigment epithelium as occurs in basal linear deposits. These deposits do not appear to be UC or EC. Laser photochemical injury of the retinal pigment epithelium may result in the appearance of BlamD-like deposits in eyes with electron-lucent debris. The BlamD-like deposits in this model are similar to the basal laminar deposits that occur in age-related macular degeneration., Clinical Relevance: This is an animal model of ultrastructural BlamD-like material in Bruch membrane that is very similar to the deposits that occur in age-related macular degeneration.

This study aimed to investigate uptake dynamics and retinal tolerance of phosphorothioate oligonucleotides (PS-oligos) following subretinal injection. A fluorescent-labeled PS-oligo (FL-oligo) with random sequence was administered into the subretinal space of rat by transsclera-choroid-retinal pigment epithelium (RPE) injection at doses of 0.129, 1.29, and 12.9 microg in 2.0 microl solution. The uptake dynamics were evaluated by fundus fluorescent photography in real time and by fluorescence microscopy using flat mounts and cryosections. Immunophenotyping for CD4+, CD8+ cytotoxic lymphocytes, and CD68+ macrophages was performed to assess cellular infiltration in the retina. In addition, the FL-oligo was injected subretinally in a rat model of choroidal neovascularization (CNV) for direct delivery into the site of CNV. Subretinal administration of FL-oligo resulted in both dose-dependent and time-dependent distribution in the retina, where it accessed the RPE and all layers of the neuroretina. CD4+, CD8+ cytotoxic lymphocytes, and CD68+ macrophages were observed at the site of needle penetration. However, in areas far from the injection site where the FL-oligo appeared strongly, cellular infiltration was absent, and the retinal morphology was preserved very well. The FL-oligo was successfully delivered into the site of intense laser photocoagulation. It was predominantly localized to the RPE, macrophages, and some choroid cells and remained detectable for at least 56 days after injection. Our results demonstrate for the first time that subretinal injection efficiently introduced PS-oligo into the RPE and neuroretina with an acceptable level of safety. Subretinal administration of antiangiogenic oligonucleotides may hold great potential for the treatment of CNV.

Aim: To determine interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) expression in response to mechanical injury in human retinal pigment epithelial (HRPE) cells., Methods: Enzyme linked immunosorbent assay (ELISA) was performed to determine IL-8 and MCP-1 secretion by HRPE cells after mechanical denudation. IL-8 and MCP-1 mRNA expression by HRPE cells was assessed using semiquantitative RT-PCR. The effects of immunosuppressive drugs, dexamethasone (DEX) and cyclosporin A (CSA), as well as immunosuppressive cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10), and interleukin 13 (IL-13), on chemokine expression in HRPE cells after denuding injury were analysed., Results: Mechanical injury induced HRPE IL-8 mRNA and IL-8 secretion. Although MCP-1 mRNA was enhanced slightly after denuding injury, MCP-1 secretion was not increased. DEX and CSA inhibited HRPE chemokine expression after injury. IL-4 and IL-13 enhanced IL-8 and MCP-1 production by HRPE cells after injury while IL-10 had no effect., Conclusions: These results suggest that IL-8 may be involved in retinal inflammatory responses to injury and that DEX and/or CSA treatment may help control the inflammatory components of retinal diseases such as proliferative vitreoretinopathy.

Background: The development of tears of the retinal pigment epithelium (RPE) has classically been described with or without choroidal neovascularization (CNV) or after laser treatment. Tangential shear forces within the RPE or CNV are usually considered to cause the dehiscence., Methods: Three patients with CNV and spontaneous RPE tear and additional vitreomacular traction were examined by fluorescein angiography (FA), optical coherence tomography (OCT) and kinetic ultrasound., Results: From the pre-tear to the tear stage a sudden decrease in vision was observed. Fluorescein angiographic images demonstrated RPE-tear formation with blocked filling in the area of the contracted RPE and a well-demarcated hyperfluorescence in the bed of the torn RPE. OCT-scans demonstrated vitreomacular traction at the foveal area in all three cases. Kinetic ultrasound revealed vitreous attachments at the optic disc and fovea., Conclusion: Magnitude, variation of mechanical forces, and the continuous shear stress of the aged vitreous gel transmitted across vitreoretinal attachments may cause a chronic stimulus to retina and RPE. Vitreomacular traction may contribute to the subsequent formation of RPE tears via mechanical or cell mediator pathways.

Purpose: To describe two patients who developed a retinal pigment epithelial tear after transpupillary thermotherapy for choroidal neovascularization., Method: Case reports., Results: Retinal pigment epithelial (retinal pigment epithelium) tear developed in 2 (8%) of 25 eyes after transpupillary thermotherapy for occult choroidal neovascularization associated with age-related macular degeneration. In both eyes, the retinal pigment epithelium tear developed between the treatment session and first post-treatment examination. In both eyes, the visual acuity was unchanged, but the complication of retinal pigment epithelium tear may result in decreased visual acuity when transpupillary thermotherapy is performed in an eye with good initial visual acuity., Conclusion: Retinal pigment epithelium tear appears to occur more frequently after transpupillary thermotherapy for poorly defined choroidal neovascularization than after conventional laser photocoagulation for poorly defined choroidal neovascularization.

Background: A peripheral retinal pigment epithelial tear and an extensive exudative retinal detachment caused by choroidal leakage from the denuded Bruch's membrane are extremely rare. A peripheral retinal pigment epithelial tear has not been reported in an eye with retinochoroidal folds after blunt ocular trauma., Methods: Case report., Results: The course of a large nasal peripheral retinal pigment epithelial tear that occurred after blunt ocular trauma in a patient with retinochoroidal folds was followed. The inferior retinal detachment caused by leakage from the denuded Bruch's membrane following the development of the tear gradually worsened. Initial treatment with cryotherapy was ineffective, but the retinal detachment eventually resolved after the patient underwent sclerectomy and sclerostomy., Conclusion: A large peripheral retinal pigment epithelial tear can occur in patients with retinochoroidal folds following blunt ocular trauma, and extensive retinal detachment can be induced. Sclerectomy and sclerostomy can be beneficial in patients with an extensive exudative retinal detachment caused by choroidal leakage from the denuded Bruch's membrane.

Objective: To observe the protective effect on the intercellular communication of retinal pigment epithelial (RPE) cells of dexamethasone (Dex) and verapamil (Ver) at different concentrations after laser photocoagulation., Method: Ten pig eyes were used to culture pig pigment epithelium cells. Use different concentrations of Dex and Ver to incubate cultured RPE cells 2 hours before laser coagulation, and then measure the intercellular communication function of confluent cells surrounding the coagulation spots after photocoagulation., Result: 125 mg/L Dex and 20 mg/L Ver could protect the intercellular communication of RPE cells under laser photocoagulation. The high concentration of drugs had better result., Conclusion: Both Dex and Ver can preserve the intercellular communication in vitro. The protective capacity is related to the concentration of drug.

Objective: To study the effects of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and 5-fluorouracil (5-Fu) on the cell migration and proliferation., Methods: Phase-contrast microscopy, cell proliferation assay and wound -closure were used to study the process of cell proliferation and wound healing in a model of human retinal pigment epithelial (RPE) cell damage., Results: It was found that EGF mainly stimulated proliferation and the migration of individual RPE cells from the wound edge, and induced cellular elongation, while bFGF mainly promoted proliferation and spread of the confluent monolayer into the wound defect, and induced enlargement and flattening of cells. But the effects of EGF, bFGF on wound closure were not very significant; 5-Fu inhibited the spread and proliferation of RPE cells, but had no effects on cell migration., Conclusions: EGF and bFGF have no significant effects on wound-healing, perhaps their effects on cell morphology are very important in cell transformation in proliferative vitreoretinopathy (PVR), and 5-Fu can only be a subsidiary drug to prevent PVR.

To investigate changes in retinal pigment epithelial (RPE) cells during wound healing, we evaluated the deposition of newly synthesized extracellular matrix (ECM) over time during wound healing in rat RPE cultures. We also estimated the effect of growth factors on the healing rate and ECM synthesis. After preparing rat RPE cell sheet cultures, we made round 1-mm defects in the cultures. Fibronectin, laminin, and collagen IV synthesis were evaluated with immunocytochemistry every 12 hours after wounding. S-phase cell distribution was analyzed every 12 hours by 5-bromodeoxyuridine uptake. We added either platelet-derived growth factor (PDGF), epidermal growth factor (EGF), or transforming growth factor- beta2 (TGF-beta2) to cultures at concentrations of 1, 10, and 100 ng/mL and immunocytochemically analyzed the effects on ECM and estimated the rate of wound closure. Although approximately 50% closure was achieved 24 hours after wounding, fibronectin deposits first appeared at that time. Laminin and collagen IV were first detected at 36 hours and fibronectin staining had extended toward the wound center. S-phase cells were distributed in concentric rings that moved centripetally over time and corresponded to the leading edge of the area stained with anti-ECM antibodies. TGF-beta2 enhanced ECM deposition, but EGF and PDGF did not. TGF-beta2 decreased the healing rate in a dose-dependent manner, whereas PDGF promoted wound closure. EGF enhanced closure at the highest concentration only. In summary, wound healing in RPE may be initiated when cells at the wound edge slide or migrate toward the wound center, which is followed by cell proliferation and then ECM synthesis. ECM components may be produced in a specific sequence during healing. TGF-beta2 may promote RPE cell differentiation, and PDGF may enhance proliferation during wound healing of the RPE.

The purpose of this study was to determine the threshold energy for light-induced functional damage of the retinal pigment epithelium at various wavelengths. Retinas of 58 pigmented and 21 albino rabbits were exposed to low intensity broadband blue light (400-520 nm), yellow light (510-740 nm), and narrowband blue light (408, 417, 439, 455, 485, 501 nm, respectively; deltalambda = 10-13 nm). The intensity values were 50, 280, and 5 mW x cm (-2), respectively, and the illumination time was 0.5 up to 5 h. The cumulative dose of light energy was calculated from these data (J x cm(-2)). The blood-retinal barrier dysfunction was evaluated in vivo using fluorophotometry to measure the leakage of fluorescein into the vitreous after intravenous injection and in vitro using light and electron microscopy after an in vivo intraarterial injection of horseradish peroxidase (HRP). The threshold energy for fluorescein leakage was 50 J x cm (-2) for blue light and 1,600 J x cm(-2) for yellow light. After broadband blue light exposure, the HRP reaction product was seen in the cytoplasm of the retinal pigment epithelium (RPE) cells and in the subretinal space but only if fluorescein leakage had been observed. Threshold energy and fluorescein leakage as a function of light energy were similar for albino and pigmented rabbits (P > 0.5). Only after yellow light exposure in excess of 3,700 J x cm(-2) was fluorescein leakage found. In that case complete disruption of the RPE was seen, but no HRP was observed in the RPE cytoplasm. Of the narrow-band blue light exposures, only that at lambda = 418 nm caused a significant increase in fluorescein leakage; the threshold energy was 18 J x cm(- 2). Blue light was found to be at least 30 times more efficient than yellow light in causing dysfunction of the blood-retinal barrier. The most efficient wavelength was 418 nm, corresponding with the absorption spectrum of cytochrome c oxidase. Melanin seemed to play no role. The presence or absence of melanin in the RPE appeared to have no influence on the threshold energy.

Retinal light damage is influenced by the body temperature during exposure, but previous studies do not agree on the magnitude of the effect. A study in rats with broadband green light reported a much larger effect than a study with 380 nm light. The present study set out to clarify whether the spectral composition of the damaging light is responsible for this discrepancy by using 488 nm instead of 380 nm light. Wavelengths in the range of 470-550 nm are known to produce a different damage type than 380 nm. Small patches of retina of anesthetized rats were exposed to 488 nm radiation of an argon ion laser. Body temperature was varied between 30 and 40.5 degrees C. Three days after irradiation, the retina was inspected by funduscopy and prepared for light microscopy. The dose of radiation needed for a just visible change in fundo decreased by 6% per degree increase in body temperature. Damage was mainly found in the retinal pigment epithelium. Temperature had no effect on damage morphology. The temperature effect at 488 nm is much smaller than reported for broadband green light. We conclude that the spectral composition of the damaging light is not responsible for the discrepancy on the magnitude of the temperature effect. Other differences between the studies must be responsible, such as difference in retinal irradiance levels.

Objective: To examine the scanning (SEM) and transmission (TEM) electron microscopic features of an in vivo rabbit model of retinal pigment epithelial (RPE) wound healing., Methods: Hydraulic debridement of the RPE was performed in one eye of each of 35 pigmented rabbits using a pars plana vitrectomy approach. Five of the 35 eyes were examined by either SEM or TEM on each of the following postoperative days: 0, 2, 4, 7, 14, 28 and 56., Results: TEM revealed that hydraulic RPE debridement results in only focal damage to the RPE basement membrane portion of Bruch's membrane and that this damage is repaired by day 7 without ultrastructural sequelae. SEM and TEM disclosed that the RPE cells at the margin of the debrided bed become flattened and enlarged and evolve a cytoskeletal reorganization with altered apical-basal polarity consistent with the development of a migrating phenotype. This is followed by gradual restoration to a more normal stationary RPE phenotype after initial closure (reepithelialization) of the RPE defect on day 7. RPE hyperplasia also occurs and may contribute to this repair process. Tight junctions are re-established among the apical surfaces of monolayered and multilayered RPE cells by day 7, coinciding with the restoration of the blood outer retinal barrier., Conclusion: Hydraulic debridement of the RPE in vivo is a useful investigational model that provides important insight into the pathogenesis of outer retinal disorders and their treatment with such techniques as submacular surgery or RPE transplantation.

The study proposes to analyze the lesions show to the retina level of the rat exposes to light of an operate microscope Zeiss Op Mi 220 (without filters). The conditions of the experiment was created such as the photochemical effect of the radiation to predominate more than thermic effect. Rat's retinae was visualized through photonic and electronic microscopy. The images show that the maximal lesions are situated to the level of the retinal pigment epithelium and of photoreceptors cells. The histological aspects presume the action of the free radicals in the production of the lesions.

Purpose: To evaluate some RPE cell functions, such as wound healing, in a preparation more similar to in situ conditions, we developed a method to obtain and culture retinal pigment epithelial (RPE) cells as a sheet. And we assessed the effects of fetal bovine serum (FBS) on the rate of RPE wound healing., Methods: We prepared RPE sheet cultures by incubating rat eyes in 0.1% proteinase K for 13 min, peeling away the neural retina-RPE complex, and then incubating the tissue for 1 h to promote spontaneous separation of the RPE sheet from the retina. After several days of incubation, the cultured sheets of RPE cells were examined by phase-contrast microscopy, scanning and transmission electron microscopy and immunocytochemistry. We made round defects 1 mm in diameter in cultured RPE sheets and estimated the rate of wound closure in media with different concentrations of FBS (0 to 10%)., Results: The RPE cells cultured in sheets retained their in situ features, including microvilli, tight junctions and gap junctions, and the distribution of actin and cytokeratin filaments. A wound was noted to close with restoration of a polygonal configuration. The rate of wound closure depended on serum concentration in the culture medium; when supplemented with 10% fetal bovine serum, wound closure was complete in approximately 40 h., Conclusions: The RPE sheet-culture technique we developed thus provides a suitable model for studying such RPE cell functions as wound healing or phagocytosis.

Background and Objective: The immediate thermodynamic effects of absorption of a laser pulse in the retina are theoretically studied to understand underlying physical damage mechanisms at threshold fluences. Damage is most likely to occur at threshold levels in the retinal pigment epithelium due to the strong absorption by the melanosomes., Methods: The retinal pigment epithelium is modeled as an aqueous environment with absorption occurring at small spherical sites with absorption coefficients representative of melanosomes. For laser pulse durations of less than 10(-6) seconds, heat conduction is negligible during energy deposition and the resulting large energy density in the melanosomes will cause vaporization of the medium immediately surrounding a melanosome., Results: We developed expressions for calculating the size of bubbles produced as a function of pulse characteristics and melanosome properties. We show that for pulse durations between 10(-6) and 10(-9) seconds, bubble formation will occur for laser fluences that are smaller than those required to cause Arrhenius-type thermal damage., Conclusion: Bubble formation is likely to be the mechanism of threshold damage to the retina for laser pulses durations in the time regime between 10(-6) and 10(-9) seconds.

Several systems of microfilaments (MF) associated with adherens-type junctions between adjacent retinal pigment epithelial (RPE) cells and between these cells and the substratum play an important role in maintaining the integrity and organization of the RPE. They include prominent, contractile circumferential MF bundles that are associated with the zonula adherens (ZA) junctions. In chick RPE, these junctions are assembled from smaller subunits thus giving greater structural flexibility to the junctional region. Because the separation of the junctions requires trypsin and low calcium, both calcium-dependent and -independent mechanisms are involved in keeping adjacent RPE cells attached to one another. Another system of MF bundles that crosses the cell at the level of ZA junctions can be induced to form by stretching the epithelium. The MF bundles forming this system are oriented in the direction in which the RPE is stretched, thereby preventing the overextension of the cell in any one direction. The system may be useful as an indicator of the direction in which tension is experienced by RPE during development of the eye, in animal models of disease and during repair of experimentally induced wounds. Numerous single-cell wounds resulting from death of RPE cells by apoptosis at various stages of repair are normally present in developing chick and adult mammalian RPE. These wounds are repaired by the spreading of adjacent RPE cells and by the contraction of MF bundles oriented parallel to the wound edge, which develop during this time. As a result of the spreading in the absence of cell proliferation, the RPE cells increase in diameter with age. Experimentally induced wounds made by removing 5-10 RPE cells are repaired by a similar mechanism within 24 h. In repair of larger wounds, over 125 microns in width, the MF bundles oriented parallel to the wound edge characteristic of spreading cells are later replaced by stress fibers (SFs) that run perpendicularly to the wound edge and interact with the substratum at focal contacts (FCs) as RPE cells start to migrate. Cell proliferation is induced in cells along the wound edge only when the wounds are wide enough to require cell migration. In the presence of antibodies to beta-1-integrins, a component of FCs, cell spreading is not prevented but both cell migration and cell proliferation are inhibited. Thus, only the organization of the cytoskeleton characteristic of migrating RPE cells that have SFs that interact with the substratum at FCs, is associated with the induction of cell proliferation.

We studied the morphological effects of human interferon-beta on repair of the retinal pigment epithelium (RPE) after moderate dye laser photocoagulation in monkey eyes. In the control eyes, RPE cells were proliferating towards the center from the margin of the laser burn 3 days after photocoagulation. At day 14 after photocoagulation, a newly formed monolayer of RPE cells covered Burch's membrane to repair the lesion. In the eyes treated with interferon-beta by systemic administration, RPE cells had proliferated remarkably 3 days after photocoagulation. The RPE cells proliferated to form multiple layers on Burch's membrane even at day 14 after photocoagulation. These results suggest that interferon-beta promotes the proliferation to repair damaged RPE.

Objective: To evaluate experimentally the conditions necessary for the formation of serous detachments., Methods: Selective injury to the retinal pigment epithelium (RPE) and choriocapillaris was produced in cats using weak laser burns and intense diffuse light, with or without photosensitization with rose bengal. The fundi were analyzed by observation, fluorescein angiography, and histologic examination., Results: Injuring the RPE alone did not cause detachments. Focal injury to the RPE and choriocapillaris caused moderate detachment only when an area surrounding the focal leakage site had been subjected to light damage. Diffuse injury to the RPE and choriocapillaris caused broader detachments., Conclusions: Three conditions are necessary for serous detachments to form: (1) a source of fluid pressure, (2) a defect in the blood-retinal barrier (entry site), and (3) an area of impaired fluid transport beyond the site of leakage (if fluid is to accumulate over a broader area).

Purpose: In vitro and animal experiments were performed to evaluate the character of retina and pigment epithelium (RPE) damage induced by ultrasonic stream from the tip of a phacofragmentor and to establish the protective properties of perfluorocarbon liquid (PFCL)., Methods: During mechanical vitrectomy in 12 rabbit eyes, the retina were exposed to ultrasound from different distances and with different powers, with and without PFCL. Electron microscopic examination was then performed to assess damage., Results: Ultrasound failed to penetrate the layer of PFCL in vitro. In eyes not injected with PFCL, exposure to the stream from 2 mm and 4 mm at both 50% and 100% powers led to retinal hole formation within 45 to 155 seconds. Damage to the RPE was found in the projection of the hole and within 1 mm from its edge under intact retina. After exposure from 6 mm and in eyes injected with PFCL, the retina and RPE were unchanged., Conclusion: It is concluded that the ultrasonic stream from a phacofragmentor may damage the retina sufficiently to cause tears, but that the interface between perfluoro-n-octane and intraocular fluid provides a reflective surface that protects the posterior pole from the stream induced by ultrasound.