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To compare the efficacy of 2 doses of intravitreal ziv-aflibercept (IVZ) with intravitreal bevacizumab (IVB) in the treatment of center-involved diabetic macular edema (DME) at 12 weeks.Three-armed, double-blind, randomized clinical trial.Eyes with center-involved DME.In this trial, 123 eyes with DME were randomly assigned to 3 injections of 1.25 mg IVZ, 2.5 mg IVZ, and 1.25 mg IVB every 4 weeks. Complete ophthalmologic examination and central macular thickness (CMT) measurement by optical coherence tomography were performed every 4 weeks up to 12 weeks.Change in best-corrected visual acuity (BCVA) at 12 weeks.Although no significant difference was evident between the 2 ziv-aflibercept groups at 12 weeks, the BCVA change was significantly better in the ziv-aflibercept 1.25 mg group than in the IVB group at the 12-week visit (P = 0.021). In regard to CMT changes, there was no significant difference between the 2 ziv-aflibercept groups; however, a significantly greater reduction in CMT was observed in the ziv-aflibercept 2.5 mg group compared with the IVB group at 12 weeks (P = 0.037). Subgroup analysis disclosed no difference in BCVA outcomes at 12 weeks among the groups in the eyes with baseline BCVA ≥20/50. In the eyes with baseline BCVA20/50, the improvement was significantly better at 12 weeks in the ziv-aflibercept 1.25 mg group compared with the IVB group (P = 0.011).The 12-week results of this trial disclosed that both 1.25 mg and 2.5 mg doses of IVZ and IVB demonstrated BCVA improvement over baseline in the treatment of center-involved DME. However, a stronger effect of IVZ compared with IVB in terms of both visual acuity improvement and macular thickness reduction was detected in the eyes with initial BCVA20/50. Longer-term efficacy and safety data will be needed to understand the role for this drug in practice.

This article describes a feasibility study of a novel trans-scleral tonometer based on the use of an instrumented form of digital palpation tonometry. Similar to manual digital palpation tonometery, trans-scleral tonometer utilizes two force probes offset by a fixed distance. Force indentation data from these probes have been shown to correlate with the intraocular pressure (IOP) of the eye. Enucleated porcine eyes were used to experimentally validate the approach. The observed hysteresis in the force data was analyzed using an analytical model that accounts for the outflow of the aqueous humor. The predictions of the model indicate that the primary reason behind the observed hysteresis is stress relaxation (accommodation) in the visco-elastic corneo-scleral shell. Experimental data from eye distention and indentation tests were then used to infer the conditions under which the novel tonometer would be expected to have an accuracy of ±1 mmHg. Analysis of the data shows that indentation rates should be kept below 0.5 mm/s for a pressure range of 10-35 mmHg. Two commonly used pressure control protocols were tested in an effort to ensure accurate IOP values during the palpation tests. Due to the large increase of IOP during digital palpation, the trans-scleral (intra-vitreous) pressurization was found to be inadequate, leading to clogging of the line by the displaced vitreous. No such problems were identified when the eye was pressurized through the cornea and into the anterior chamber. Force data from multiple palpation experiments are used to generate calibration curves for a two-probe conceptual tonometer. The calibration showed that a 10 mN of force variation corresponds to 1 mmHg of IOP change. A possible implementation using a contoured facial mask is also presented.

Oxygen saturation (OS) levels in the juxta-papillary retina particularly inferotemporal retina were investigated in open-angle glaucoma (OAG) patients as well as normal subjects. Fifty-six eyes of 56 OAG Japanese patients and 20 eyes of 20 age-matched normal subjects were recruited for the study. OAG eyes (56) were subdivided into two groups: 15 eyes of low-tension (LT) subgroup and 41 eyes of high-tension (HT) subgroup. The average of age of the LT, HT subgroup and normal group were 60.5, 55.9 and 52.6 years, respectively. OS levels in the retina were measured using a Fourier transform-based spectral retinal imaging (SRI) system (Retinal Cube; ASI Co. Migdal Hemak, Israel), with which OS levels in the fundus could be computed at every pixel point of a 35 degrees fundus image. We calculated OS levels at five points in the retina near the optic disc and retinal arteries and veins in all eyes. The OS levels were also compared with the results analyzed using Humphrey visual field Analyzer with the program 30-2 SITA. At the superior and nasal juxta-papillary retinal points, OS level of the LT subgroup showed significant decrease as compared with the HT subgroup and the normal group ( p = 0.048–0.009). The LT and the HT subgroups were significantly lower than the normal group at the inferotemporal and the average of the retinal points ( p = 0.047–0.001). There were no statistically significant differences among the three groups in regards to the OS in the retinal artery. There was a statistical significant correlation between the mean of total deviation of the 17 points in the upper arcuate area and OS of the inferotemporal point ( p = 0.018), and between mean deviation and the average of OS of the inferotemporal and the superotemporal point ( p = 0.037) in the HT subgroup. However, there was no significant correlation in the LT subgroup. OS levels in the retina were especially decreased in the low-tension glaucoma subtype. There was a correlation between the visual field defect and OS in the HT eyes in the inferotemporal region. OS measurement may be a novel adjunct to study glaucoma patients.

Objectives Pharmacotherapeutics has begun to play an increasingly important role in the management of patients with neovascular age-related macular degeneration (AMD). Because micro- and nano-particulates are currently being evaluated as a potential drug-delivery option for AMD patients, the purpose of this analysis was to describe how micro- and nano-particulates have been used experimentally and what their potential clinical applications may be. Findings Micro- and nano-particulates have been used primarily on a pre-clinical basis as new drug-delivery devices in experimental models of neovascular AMD. Conclusions It is likely that micro- and nano-particulates will become an important component of targeted clinical pharmacotherapeutics in patients with neovascular AMD.

Objective To compare the efficacy of the classic treatment of ocular toxoplasmosis (pyrimethamine, sulfadiazine, and prednisolone) with a regimen consisting of trimethoprim/sulfamethoxazole (co-trimoxazole) plus prednisolone. Design Prospective randomized single-blind clinical trial. Participants Fifty-nine patients with active ocular toxoplasmosis were randomly assigned to 2 treatment groups: 29 were treated with pyrimethamine/sulfadiazine, and 30 patients received trimethoprim/sulfamethoxazole. Intervention Treatment consisted of 6 weeks' treatment with antibiotics plus steroids. Antitoxoplasmosis antibodies (immunoglobulin M [IgM] and IgG) were measured using an enzyme-linked immunosorbent assay. Main Outcome Measures Changes in retinochoroidal lesion size after 6 weeks' treatment, visual acuity (VA) before and after intervention, adverse drug reactions during follow-up, and rate of recurrence. Results Active toxoplasmosis retinochoroiditis resolved in all patients over 6 weeks' treatment, with no significant difference in mean reduction of retinochoroidal lesion size between the 2 treatment groups (61% reduction in the classic treatment group and 59% in the trimethoprim/sulfamethoxazole group, P = 0.75). Similarly, no significant difference was found in VA after treatment between the 2 groups (mean VAs after treatment were 0.12 logarithm of the minimum angle of resolution [logMAR] [20/25] in the classic treatment group and 0.09 logMAR [20/25] in the trimethoprim/sulfamethoxazole group, P = 0.56). Adverse effects were similar in both groups, with one patient in each suffering from any significant drug side effects. The overall recurrence rate after 24 months' follow-up was 10.16%, with no significant difference between the treatment groups ( P = 0.64). Conclusions Drug efficacies in terms of reduction in retinal lesion size and improvement in VA were similar in a regimen of trimethoprim/sulfamethoxazole and the classic treatment of ocular toxoplasmosis with pyrimethamine and sulfadiazine. Therapy with trimethoprim/sulfamethoxazole seems to be an acceptable alternative for the treatment of ocular toxoplasmosis.

This review outlines the applications of liposomal formulations in ophthalmology. In ophthalmology, liposomes have been used to treat disorders of both the anterior and posterior segments. These include dry eyes, keratitis, corneal transplant rejection, uveitis, endophthalmitis, and proliferative vitreoretinopathy. Liposomes also have shown promise as vectors for genetic transfection and monoclonal antibody-directed vehicles. Furthermore, heat-activated liposomes have spurred research in focal laser and heat-induced release of liposomal drugs and dyes for selective drug delivery. These techniques have been useful in selective tumor and neovascular vessel occlusion, angiography, and retinal and choroidal blood-flow studies. Although verteporfin is the only liposomal drug currently approved for use in the eye, the benefits of liposomes will likely be applied widely in all treatment, diagnostic, and research aspects of ophthalmology in the future.

Objective To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. Design Experimental animal study. Animals Pigmented and nonpigmented rabbits; rhesus monkeys. Intervention The hydrophilic photosensitizer, mono-l-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. Main outcome measures Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. Results Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. Conclusions Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

We report a rare clinical case of unilateral ciliary body teratoid medulloepithelioma presented first with infantile cataract, subsequently masquerading as chronic granulomatous anterior uveitis, followed by appearance of a tumour over the iris surface.Diagnosis of the tumour in the early stages allows proper management and avoids enucleation.

To study the toxicity of intraocular lidocaine, bupivacaine, and a combination of the two anesthetics.The right eyes of 34 rabbits were divided into eight groups, and each was injected intravitreally with 0.2 ml of lidocaine hydrochloride in a 2%, 1%, 0.5%, or 0.25% concentration, or bupivacaine hydrochloride in a 0.75%, 0.5%, or 0.25% concentration, or a 1:1 mixture of lidocaine 2% and bupivacaine 0.75%. The left eyes of four of these rabbits received an injection of balanced saline solution. Electroretinograms were recorded before injection and 30 minutes, 90 minutes, 3 hours, 6 hours, 24 hours, and 1 week after injection. The amplitude and the implicit time were analyzed. The rabbits were killed 1 week after injection and the eyes evaluated histologically.No adverse clinical reaction and no histologic abnormality was observed in any of the nine groups after injection. The a- and b-waves of the electroretinograms in the control group injected with balanced saline solution, and the a-waves of the experimental groups that received injections of lidocaine, bupivacaine, or the mixture, were normal. The b-waves of the experimental groups demonstrated a marked decrease in the amplitude and an increase (P.05) in the implicit time after intravitreal injection. Electroretinogram responses recovered within 24 hours.Intravitreal injection of 0.2 ml of lidocaine up to 2%, or of bupivacaine up to 0.75%, and the mixture of lidocaine 2% and bupivacaine 0.75%, induced reversible electroretinogram changes in the rabbit retina. No histologic abnormalities were observed.

Objective: The purpose of the study was to determine the predictors of success and evaluate the use of perfluoroperhydrophenanthrene as an intraoperative and postoperative tool in the management of giant retinal tears in a multicentered collaborative study. Design: Multicentered prospective case series. Participants: Twenty-three centers consecutively enrolled 162 eyes of 161 patients with retinal tears 90° or greater in circumferential extent. Intervention: Perfluoroperhydrophenanthrene was used as an intraoperative surgical adjunct in all cases and left after surgery in 16 eyes (9.9%). Main Outcome Measures: Retinal reattachment and visual acuity. Results: Intraoperative reattachment was achieved in 158 eyes (97.5%); 147 eyes (90.7%) remained attached at their most recent follow-up. Seventy-nine eyes (48.8%) experienced an improvement in their visual acuity, 26 eyes (16.0%) remained unchanged, and 57 (35.2%) worsened. Recurrent retinal detachment occurred in 80 patients (49.4%). Other significant postoperative complications included cataract formation in 20 (39.2%) of 51 eyes, macular pucker in 12 (7.4%), corneal decompensation in 10 (6.2%), and hypotony (intraocular pressure equal to or less than 5 mmHg) in 9 (5.6%). A chi-square analysis of preoperative characteristics showed that hypotony ( P = 0.007), macular detachment ( P = 0.020), a history of cataract extraction ( P = 0.003), poor visual acuity ( P = 0.000), giant tear extent greater than 180° ( P = 0.004), and higher grade proliferative vitreoretinopathy ( P = 0.000) all predicted a poor visual outcome. Vitreon (Vitrophage, Inc., Lyons, IL) was left in 16 eyes (9.9%) for an extended postoperative retinal tamponade for between 3 and 1034 days (mean, 87.2 days). The Vitreon was well tolerated, and these eyes experienced a similar outcome and rate of retinal reattachment to the rest of the group. Conclusions: Vitreon is a safe and useful adjunct to pars plana vitrectomy in the management of giant retinal tears and may, additionally, be the perfluorocarbon liquid that can be used most safely as a temporary postoperative tool for extended retinal tamponade, reinforcing its role as a useful adjunct in the management of these complex retinal detachments.

Purpose Evaluation of ocular tissue reactions to 670-nm diode laser. Methods Twelve eyes of 12 pigmented rabbits were used. Transscleral contact laser delivery of a new 670-nm diode laser was used to produce retinal laser lesions in four rabbits; endolaser application of this laser produced photocoagulation of the retina in another four rabbits; and ciliary body lesions were produced by transscleral application of this laser in a third group of four rabbits. The rabbits were killed either 2 days or 1, 3, or 6 weeks later; lesions were evaluated by gross examination and histology. Results The mildest visible retinal lesions were produced by transscleral contact application at 0.2 J (2 seconds, 100 mW); explosive lesions began at 0.6 J. The mildest visible lesions were produced by endolaser application at 50 mW (spot size, 0.5 mm); intensive reactions started to occur at 300 mW, but no explosive lesions were produced below 600 mW. With contact transscleral application, substantial ciliary body reactions occurred at 0.5 and 1.0 J. Histologic examination disclosed destruction of the outer retina, pigment epithelium, and parts of the choroid in mild lesions, and of all retinal layers in the intense lesions. Conclusions In this experimental study, the 670-nm diode laser appears to be a promising modality for laser photocoagulation of the retina and ciliary body.

Intravitreal drug delivery has been developed to treat posterior segment diseases because the blood-ocular barrier prevents treatment by topical, systemic, or subconjunctival routes from attaining therapeutic levels in the vitreous. Endophthalmitis, uveitis, proliferative vitreoretinopathy, and viral retinitis are treated by intravitreal injection. Efforts to sustain drug delivery have included encapsulation of drugs in liposomes (made of lipids) or microspheres (made of polymers). In many instances the drug's toxicity to the retina was reduced and the clearance time was slowed. However, these methods cause clouding of the vitreous and can prolong drug delivery for only one month. Implantable devices have been used, such as an osmotic minipump, a drug pellet coated with polyvinyl alcohol and ethylene vinyl acetate, and polysulfone capillary fiber. Biodegradable devices are under investigation, including a drug matrix and a porous reservoir system, both made of polymers; these devices would not require surgical removal.

Purpose: To measure blood flow in the retinal circulation and optic nerve head capillaries with an innovative fluorescent vesicle system. Methods: Carboxyfluorescein was encapsulated into liposomes; the vesicles ranged from 0.1 to 2 µm in diameter. After intravenous injection of the liposome suspension, the fundus was viewed using a scanning laser ophthalmoscope. Images of the fundus showing circulating liposomes were stored on videotape. An image analyzing system was used to digitize the captured video frames and transfer them to a computer's hard disk for permanent storage. Software developed in the authors' laboratory allowed them to overlay multiple video frames to create a single image that provided a visible record of the path taken by a particular vesicle in a given time period. The information on this image was used to calculate the velocity of the vesicle, and hence the velocity of the blood flow in the vessel. Results: With this system, individual liposomes as small as 100 nm were visible in all retinal vessels (arteries, capillaries, and veins). Quantitative analysis of vesicle movement in the major retinal vessels of the cynomolgus monkey yielded an average velocity of 9.33 ± 1.67 mm/second in a large vein (diameter, 130 µm) and 16.10 ± 5.7 mm/ second in a large retinal artery (diameter, 64 µm). The average velocity in the macular capillaries was 0.76 mm/second (range, 0.45-1.33 mm/second), whereas the average velocity in the optic nerve head capillaries was 1.39 mm/second (range, 0.96-2.25 mm/ second). Conclusion: The fluorescent vesicle system can be used for simultaneous measurement of blood flow in the retinal arteries, veins, and capillaries of the macula and optic nerve.

Sudden phakic pupillary block occurred immediately upon cortical cleaving hydrodissection during cataract surgery in two patients. We believe this unique complication is related to the recent introduction of viscoelastics with properties that enhance the maintenance of the anterior chamber during capsulorhexis. We postulate that the cause of the block was a combination of O-ring capsulocortical and iridocapsular seals that tamponade hydrodissection fluid posteriorly. Additional precipitating factors were diabetes, poorly dilating pupils, and increased vitreous pressure, which may have contributed to the sudden and irreversible nature of this block. If this complication is not recognized, an aqueous misdirection syndrome may ensue, requiring pars plana vitrectomy. Immediate mechanical breakage of the pupillary and capsular block, resulting in an immediate decrease in intraocular pressure from greater than 70 mm Hg, may cause severe retinal vascular damage. These cases stress the importance of mechanical pupil dilation to prevent this serious complication of cataract surgery.

Newborn mammals, compared to adults, are extremely resistant to the CNS effects of hyperbaric oxygenation (HBO) induced by excessive generation of reactive oxygen species. This tolerance to HBO may be related to either physiological responses or the chemical characteristics of the immature brain, including a low cerebral blood flow and energy metabolism and a low concentration of polyunsaturated fatty acids. In adult mammals the main protective mechanism against CNS oxygen toxicity, besides endogenous antioxidants, is a transient HBO-induced cerebral vasoconstriction. How cerebral vasculature reacts to HBO in the immature brain is not known. We present indirect evidence suggesting that HBO in newborn rats induces a persistent cerebral vasoconstriction concurrently with a severe and maintained reduction in ventilation. It is speculated that the outcome of these physiologic responses to hyperoxic exposures may be: (a) extension of tolerance to both CNS and pulmonary oxygen poisoning; (b) creation of a profound hypoxic-ischemic condition in vulnerable neural structures: and (c) impairement of the circulatory and ventilatory responses to hypoxic stimuli on return to air consequent development of a secondary hypoxic-ischemic condition. These hypothetical pre- and post-HBO events may set the stage for the development of some delayed neurological disorders, including the retinopathy of prematurity and the retardation of brain development in fetuses or prematurely-born infants subjected to oxygen therapy.

Background: Suprachoroidal hemorrhage may cause the expulsion of intraocular contents. Generally, cases of nonexpulsive suprachoroidal hemorrhage have a better outcome than their expulsive counterparts. Those cases with massive nonexpulsive suprachoroidal hemorrhage do better with treatment than without. Treatment modalities have included suprachoroidal hemorrhage drainage with or without intraocular volume reformation, and vitrectomy. Methods: The authors used the liquid perfluorocarbon perfluoroperhydrophenanthrene in the treatment of three patients with nonexpulsive suprachoroidal hemorrhage. The perfluorocarbon was injected into the vitreous cavity while the suprachoroidal blood was drained through anterior sclerotomies. Results: With 5 months of follow-up, complete resolution of the suprachoroidal blood was noted in all patients. All three patients had attached retinas, and postoperative visual acuities were improved over preoperative visual acuities. Conclusion: Perfluoroperhydrophenanthrene and other perfluorocarbon liquids may be beneficial in the treatment of certain cases of nonexpulsive suprachoroidal hemorrhages.

We examined the effects of ultraviolet (UV) irradiation on the release of prostaglandin E 2 (PGE 2 ) by rabbit corneal stromal cells in culture. Considerable amounts of PGE 2 were present in the media of control corneal cultures following 1, 2, 4, 8 and 24 hr of incubation. Irradiation with UV-A (320–400 nm) for 30 min resulted in more than a 50% increase in PGE 2 release. Dexamethasone inhibited PGE 2 release by corneal stromal cells. It was, however, ineffective in protecting the cells from the UV-induced release of PGE 2 .

Using immunofluorescence and immunoperoxidase procedures, we found large amounts of IgG, IgA, IgM, and IgE, as well as C1q, C3c, and C3d, in the connective stroma and within the vascular walls on eight specimens of preretinal membranes obtained from diabetic patients with proliferative retinopathy. The membranes contained many isolated human leukocyte antigen (HLA) DR- and DQ-expressing cells, and vascular endothelial cells strongly expressed class II determinants. Monoclonal antibodies to immunocompetent cells disclosed only rare B lymphocytes or suppressor/cytotoxic T cells and few monocytes. These findings confirm previous evidence of immune reactions in the pars plana of patients with proliferative diabetic retinopathy, and suggest that an autoimmune reaction is a factor in this complication. It is yet not possible to determine whether this reaction is a nonspecific consequence of the vasoproliferative processes or if it plays a direct role in the development and extension of preretinal membranes.

espanolObjetivo: Valorar la toxicidad retiniana de la doxiciclina administrada en inyecciones intravitreas. Metodo: Utilizamos catorce conejos albinos neozelandeses que dividimos en 5 grupos. Inyectamos en dos ojos cada una de las siguientes concentraciones de doxiciclina: 2.000 µg/0,1 ml; 500 µg/0,1 ml; 250 µg/0,1 ml; 125 µg/0,1 ml y 67,5 µg/0,1 ml. Dos ojos, usados como control, recibieron 0,1 ml de solucion de dextrosa al 5%. Examinamos a todos los animales antes y despues de la inyeccion con oftalmoscopia indirecta y biomicroscopia. Realizamos electrorretinogramas en todos antes de la inyeccion intravitrea y dos semanas despues; y posteriormente los animales fueron eutanizados. Se enuclearon los ojos y se prepararon para estudio histologico. Resultados: Los grupos que mostraron una disminucion significativa en los electrorretinogramas fueron los inyectados con las siguientes concentraciones de doxiciclina: 2.000 µg/0,1 ml; 500 µg/0,1 ml y 250 µg/0,1 ml. No se observaron cambios significativos en los electrorretinogramas de los inyectados con 125 y 67,5 µg/0,1 ml. No hubo signos de toxicidad retiniana en los examenes de biomicroscopia, en oftalmoscopia indirecta e histologia de los inyectados con 125 µg/0,1 ml o niveles menores de doxiciclina. Conclusion: Las inyecciones intravitreas de doxiciclina parecen seguras en un rango igual o menor a 125 µg/0,1 ml en el conejo albino. La doxiciclina intravitrea podria ser una alternativa barata y beneficiosa para el tratamiento de la endoftalmitis, especialmente frente a los staphylococcus aureus resistentes. EnglishObjective: To assess the retinal toxicity of varying concentrations of intravitreally administered doxycycline, a member of tetracycline family. Methods: Fourteen New Zealand albino rabbits, divided into 5 groups, were used for this study. The initial concentration of doxycycline (100 mg) was titrated using 5% dextrose solution to the following concentrations in a volume of 0.1 ml: 2000 µg, 1000 µg, 500 µg, 250 µg, 125 µg, and 62.5 µg. Each concentration was injected into 2 rabbit eyes. Two control eyes received 0.1 ml of 5% dextrose solution. All animals were examined before and after injection using indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography (ERG) was performed on all animals prior to the intravitreal injection and 2 weeks post-injection. The animals were re-examined at this time by indirect ophthalmoscopy and slit-lamp biomicroscopy and were then subjected to euthanasia. Their eyes were enucleated and examined using light microscopy. Results: The doxycycline injected group exhibited significant decreases in ERG of the eyes injected with 2000 µg, 1000 µg, 500 µg, and 250 µg/0.1 ml. No significant changes in the ERG were observed following the injection of lesser concentration levels. There were no signs of retinal toxicity on slit-lamp examination, indirect ophthalmoscopy, or light microscopy in all the eyes injected with doxycycline concentrations of 125 µg or lower. Conclusions: Doxycycline injected intravitreally appeared safe at concentrations of 125 µg/0.1 ml or less in albino rabbits. Intravitreal doxycycline may be beneficial, and is an inexpensive alternative drug which could be used in the treatment of bacterial endophthalmitis particularly against resistant Staphylococcus aureus organisms.

I read with interest the paper by Nishant Kumar and colleagues, I in which they cited our publication.2 However, our study refers to the prophylactic use of antibiotics during vitrectomy and not in irrigating solution in cataract extraction. We have shown clinically2 and experimentally3 that this method can work for posterior segment surgery if 1) one is dealing with an organism sensitive to the antibiotic used, and 2) the bacterial load is not high.3 The pharmacokinetics of the antibiotic in the vitreous after vitrectomy is significantly better suited for prophylaxis than that in the anterior chamber after cataract extraction. The aqueous is replaced completely in less than 2 hours, which does not provide enough time for the antibiotics to be very effective at these low concentrations. The results would be potentially different if the dosage were significantly higher (e.g., 30 pg and above for gentamicin).4 Finally, there is no absoluteness in any concept in medicine. This is especially true if the organism causing endophthalmitis is not sensitive to the drug used or if the concentration of the antibiotic is not high enough, as in this reported case.

Summary Two PVA-coated intraocular lenses were implanted. In the first case there was an acute onset of severe intraocular inflammation and dense membrane formation on the surface of the implant. The inflammation developed on the fifty-third postoperative day in a previously quiet eye. The second case demonstrated a relentless increase in intraocular inflammation that was unresponsive to medical therapy. An acute exacerbation with membrane formation occurred between the fortieth and forty-fifth postoperative days. In both cases the fibrinous membranes and the implants were removed with prompt resolution of symptoms.

The authors have developed a CW YAG laser for transpupillary coagulation. The effects of CW YAG coagulation on the retina, retinal vessels, and fovea were compared with those produced by the krypton red and argon green lasers. To produce threshold coagulative lesions in monkeys and rabbits, we needed five to ten times more energy with the CW YAG than with the krypton red or argon green lasers. Nerve fiber damage was observed only when coagulating retinal vessels with the argon green laser. At the parameters used, none of the lasers damaged the sensory retina of the fovea. The CW YAG may be used as a new mode of laser coagulation in the treatment of retinal diseases.

After laboratory evaluation of nontoxic doses of intravitreal antibiotics, 26 cases of bacterial and fungal endophthalmitis were treated by intravitreal antibiotic or vitrectomy. In 46% of all cases, visual acuity was better than 20/100, whereas 27% had light perception to 20/300 visual acuity, 4% had no light perception, and 23% of the cases were enucleated or eviscerated. Best results have been achieved when the treatment began within 36 hours after symptomatic onset of infection and when the organism involved was not to virulent. We advocate intravitreal antibiotics immediately after intracameral and vitreous tap for culture, to be followed by vitrectomy 24 hours later if the culture is positive. In bacterial endophthalamitis when the vitreous is severely involved and in cases of fungal endophthalmitis, we advocate vitrectomy plus intravitreal antibiotics as the primary procedure.

Two groups of albino rabbits received an intravitreal injection of liposome-encapsulated trifluorothymidine. One group underwent a clearance study using high-performance liquid chromatography. The results of this study demonstrated a prolonged vitreal drug level within the range of ID50 for many strains of herpesvirus and human cytomegalovirus (CMV) at 28 days after injection. The eyes of another group were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. No retinal toxicity was found.

Lasers have become an indispensable tool in management of many ocular disorders. This review describes the principles of lasers and the effects various laser modalities and wavelength modalities can produce on ocular structure. Guidelines are provided for appropriate selection of various wavelengths and prevention of complications of the laser treatment.

Twelve cases of traumatic culture-proven endophthalmitis were treated with intraocular antibiotics or in combination with vitrectomy. In 11 cases, the eyes were saved and in 10 the visual acuity was equal to or better than 20/200.

Proliferative vitreoretinopathy (PVR) is a disease process that occurs in eyes with rhegmatogenous retinal detachments and accounts for the majority of failures following retinal detachment surgery. PVR involves the uncontrolled proliferation of non-neoplastic cells capable of forming membranes, which may occur on either surface of the retina or along the detached surface of the vitreous gel. Contraction of these membranes creates tractional forces that can distort or detach the retina. Various surgical procedures have been used to repair retinal detachments associated with PVR. The results have not been encouraging in many instances. Recent efforts have been directed toward the chemical inhibition of cellular proliferation in PVR. The majority of drugs used in these studies have been antineoplastic agents that affect various phases in the cycle of cell growth.

One hundred consecutive eyes underwent vitrectomy with the disposable vitrophage via a pars plana approach. Eyes were divided into two main categories based on opacity location-in the anterior or posterior segment. Patients with posterior segment opacities had diabetic retinopathy, nondiabetic vitreous hemorrhages, retinal detachments associated with vitreous hemorrhage, bands, or membranes, and intraocular foreign bodies or silicone oil. Patients with anterior segment opacities were treated for pupillary membranes resulting from surgical trauma or perforating injuries, and for complications following cataract extraction, such as capsule breakage and vitreous loss. Postoperatively, visual acuity improved in 68% of eyes with posterior segment opacities and in 85% of eyes with anterior segment opacities. Overall, visual acuity was 20/300 or better in 45% of eyes. There were only two intraoperative retinal tears and one postoperative rhegmatogenous retinal detachment.

Two large angiomas (greater than 3 disc diameters) in two patients with von Hippel disease were removed successfully by eye wall resection. The resection of angioma in the first case resulted in improved visual acuity from counting fingers to 20/140, decreased exudates, and cessation of preoperative diffuse retinal capillary leakage observed by fluorescein angiography. The resection in the second case with pre-existing local tractional retinal detachment was tolerated well. The patient retained her preoperative visual acuity of 20/25, and retinal traction was released. Although a complicated surgical procedure, resection of large angiomas offers a good alternative therapy to tumors resistant to cryocoagulation or photocoagulation.

A 25-year-old Iranian man had undergone eye wall resection of a large von Hippel angioma to alleviate an exaggerated macular response, affording study by light and electron microscopy and immunohistochemistry before the obfuscatory effects of long-standing exudative retinal detachment, gliosis, or iatrogenic ablation supervened. We used this vantage point to assess the interrelation between the component endothelial cells, pericytes, and stromal foam cells. On the basis of staining with glial fibrillary acidic protein, factor VIII, the C3 fraction of complement, fibrinogen, and lysozyme, it is unlikely that stromal foam cells derive from glial precursors, but may represent degenerating cells, perhaps arising from a common vasoformative stem cell under hypoxic stress.

Of the results evaluated in 17 patients who had vitrectomy for aphakic vitreocorneal touch associated with corneal edema, nine patients had satisfactory results. Factors associated with a favorable outcome were as follows: (1) early vitrectomy; (2) previtrectomy visual acuity better than 6/120 (20/400); (3) uncomplicated cataract operation and postoperative course, and (4) broken rather than intact hyaloid face. Postoperative cystoid macular edema contributed to decreased visual acuity in eight of 12 patients.

Two hundred and sixty-four patients who had unilateral implant surgery and normal contralateral unoperated eyes were studied by slit-lamp anterior segment fluorophotometry. Patients tested five weeks to six months after surgery averaged 22% more fluorescein in the operated than in the unoperated eye, while those tested after six months averaged only 12% more fluorescein. Patients receiving topical indomethacin demonstrated an 11 increase in fluorescein, while those taking a placebo averaged a 33% increase. Patients with cystoid macular edema averaged a 46% increase in fluorescein compared with a 17% increase in the other patients. Twenty-seven control patients with unilaterally aphakic eyes and normal contralateral unoperated eyes, tested on an average of two years after surgery, showed essentially no increase in fluorescein in the operated eye. Fluorophotometry may be a valuable clinical tool in testing the effect of drugs on the blood-aqueous barrier and to screen patients for cystoid macular edema.

A recently developed liposome-dye method was used to make quantitative measurements of blood velocity and volumetric flow rates in the retina of the rhesus monkey. After systemic injection of a liposome-encapsulated fluorescent dye (calcein), the release of a bolus of the dye in the retina was triggered by an ophthalmic argon laser. Initially, calcein was entrapped at a high concentration and the fluorescence of the dye in the lipid vesicle was quenched. After laser exposure, the liposomes released a bolus of dye at the laser exposure site in a specific vessel of the retina. The released dye formed a well-defined, fluorescent wavefront in the exposed artery or vein. By measuring the distance the dye traveled in the vein over a set time interval, it was possible to measure blood velocity in retinal vessels of various diameters, and to calculate volumetric flow rates in those vessels.

We studied the effects of visible (400-750 nm), infrared (750-1100 nm), and ultraviolet (300-400 nm) radiation on the breakdown of the blood-aqueous barrier (BAB) in albino rabbit eyes using fluorophotometry and fluorescein-bound albumin. There was no evidence of BAB breakdown following exposure to visible (158 J cm-2) or infrared (106 J cm-2) radiation. Fluorescence was detected in the anterior chamber 15 min following ultraviolet (UV) (300-400 nm; 37 J cm-2 and 73 J cm-2) and ultraviolet-A (UV-A) (320-400 nm; 45 J cm-2 and 90 J cm-2) irradiation. This fluorescence peaked at 2 hr after irradiation. Reestablishment of the BAB, indicated by no detectable fluorescence, occurred in all animals after 24 hr. There was a significant increase in fluorescence with increasing UV-irradiation dosage in all groups (P less than 0.05). Comparison of BAB breakdown following exposure to ultraviolet 320-400 nm and 300-400 nm in the same dosage (45 J cm-2) indicated that the inclusion of shorter wavelength UV exposure produced a significantly higher degree of BAB breakdown (P less than 0.001).

Summary To overcome the problem of postoperative lens dislocation, we evaluated a new means of lens fixation. Our experimental studies in rabbits and primates demonstrated that Dacron polyethylene terephtalate induced a cellular reaction from either the anterior or posterior iris surface when placed in contact with the iris, thereby establishing a bond between the Dacron fibers and the iris. Dacron mesh can be attached to the distal portion of either the anterior or posterior loops of a Binkhorst iris clip (4-loop) lens. In the rabbit eye, lens fixation occurred within five days; in the primate eye, 30 days. When combined with silk, Dacron produced tissue ingrowth in the primate eye within 14 days. No unwanted reaction occurred in any animal with the Dacron and silk combination. Being biodegradable, the silk induced faster cellular ingrowth than the Dacron. However, Dacron, which is not biodegradable, provided a permanent means of fixation.

Uncoated intraocular lenses caused extensive corneal endothelial cell damage after in vitro contact (mean, 30.9% cell loss), whereas lenses coated with bovine submaxillary mucin type 1 caused minimal cell loss (mean 4.3%). No observable in vivo toxicity in the eye occurred when 0.1 ml of 3, 6, or 9% solution was injected into the anterior chamber. Mucin-coated lenses can be sterilized by ethylene oxide with no measurable adsorbence into the coating. Scanning electron microscopy confirmed the results from vital staining.