International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

A novel model of subretinal edema induced by DL-alpha aminoadipic acid.

In this study we described a new model of subretinal edema induced by single intraocular injection of DL-alpha-aminoadipic acid (DLAAA) that can be employed to study the mechanism of retinal edema and test the efficacy or potential toxicity of treatments. The progression of subretinal edema was evaluated by fundus photography, fluorescein angiography and optical coherence tomography for up to 4 weeks following DLAAA injection. The VEGF, IL-6, TNF-α, Occludin, ZO-1, AQP4, Kir4.1, GFAP and GS levels were examined in DLAAA models by immunostaining, immumohistochemical staining and Western blot. Additionally, bulk RNA-seq was used to detect the mechanism involved in DLAAA-induced retinal Müller cellular injuries. In vivo and vitro assays were further conducted to confirm the sequencing results. Subretinal edema was successfully induced by DLAAA in New Zealand White rabbits (1.29 mg/eye) and C57BL/6 mice (50 or 100 µg/eye). Our results demonstrated that the disruption of blood-retinal-barrier, including vascular hyperpermeability, inflammation, and Müller cell dysfunction of fluid clearance, was involved in subretinal edema formation in the model. Bulk RNA-seq and in vitro studies indicated the activation of p38 MAPK signaling pathway in DLAAA models. This DLAAA-induced subretinal edema model can be used for mechanistic studies or drug screening.

Attitudes toward ophthalmology as a prospective career among pre-clinical medical students in China.

BACKGROUND: A questionnaire was developed and administered to 450 medical students at the Xiangya Medical College, Central South University in Changsha, China to understand the attitudes among medical students in China toward different medical specialties and to find the factors that influenced their choice of career in ophthalmology. PARTICIPANTS: Fourth-year medical students in the five-year program and sixth-year medical students in the eight-year program. METHODS: All the students were asked to rate the importance of nine possible factors in choosing a specialty as their vocation and their first ranked future specialty career choice. RESULTS: When asked about the reasons for choosing to go to medical school, the top four reasons are the ability to help patients, interesting and challenging work, prestige, and job stability. When asked about the reasons for choosing a specialty, the top four reasons are the ability to find employment, financial reward, career upward mobility, and professional pressure. About the first career choice of the future specialty, for clinical medicine students, ophthalmology is the fifth ranked choice for clinical medicine students. 5.6% (five-year) and 3.4% (eight-year) of them choose ophthalmology as their top ranked specialty for their career. For anesthesia medicine and oral medicine students, most of them preferred to choose the same specialty as before. 1.5% (anesthesia) and 4.5% (oral) of them chose ophthalmology as their top ranked specialty. CONCLUSIONS: Medical students in China have numerous factors that motivate their choice in a specialty. Ophthalmology is the fifth ranked choice among clinical medicine students.

Age differential response to bevacizumab therapy in choroidal neovascularization in rabbits.

Choroidal neovascularization (CNV) in young rabbits has been shown to have a rapid, robust response after treatment with bevacizumab, an anti-vascular endothelial growth factor (VEGF) medication. This investigation evaluates an age differential response to bevacizumab in older populations of rabbits using multimodal high resolution molecular imaging. Young (4 months old) and life span (14 months old) rabbits were given subretinal injections of Matrigel and VEGF to produce CNV. All CNV rabbit models were then treated with a bevacizumab intravitreal injection. Rabbits were then monitored longitudinally using photoacoustic microscopy (PAM), optical coherence tomography (OCT), color photography, and fluorescence imaging. Chain-like gold nanoparticle clusters (CGNP) conjugated with tripeptide arginylglycylaspartic acid (RGD) was injected intravenously for molecular imaging. Robust CNV developed in both young and old rabbits. After intravitreal bevacizumab injection, fluorescence signals were markedly decreased 90.13% in the young group. In contrast, old rabbit CNV area decreased by only 10.56% post-bevacizumab treatment. OCT images confirmed a rapid decrease of CNV in the young group. CGNPs demonstrated high PAM signal in old rabbits and minimal PAM signal in young rabbits after bevacizumab, indicating CNV regression. There is a significant difference in response to intravitreal bevacizumab treatment between young and old rabbits with CNV which can be monitored with multimodal molecular imaging. Old rabbits demonstrate significant persistent disease activity. This represents the first large eye model of persistent disease activity of CNV and could serve as the foundation for future investigations into the mechanism of persistent disease activity and the development of novel therapies.

Photo-mediated ultrasound therapy for the treatment of retinal neovascularization in rabbit eyes.

OBJECTIVES: Retinal neovascularization (RNV) is the growth of abnormal microvessels on the retinal surface and into the vitreous, which can lead to severe vision loss. By combining relatively low-intensity ultrasound and nanosecond-pulse-duration laser, we developed a novel treatment method, namely photo-mediated ultrasound therapy (PUT), which holds a potential to remove RNV with minimal or no damage to the adjacent tissues. METHODS: RNV was created in both albino and pigmented rabbits (n = 10) through a single intravitreal injection with DL-α-aminoadipic acid. RNV was treated with PUT 8 weeks postinjection. After PUT treatment, animals were evaluated longitudinally for up to 6 weeks. Treatment outcomes were evaluated through fundus photography, red-free fundus photography, fluorescein angiography (FA), and histopathology. RESULTS: In both albino and pigmented rabbits, there were no leakage in the treatment area immediately after PUT treatment as demonstrated by FA, indicating the cessation of blood perfusion of the RNV in the treated area. The fluorescence leakage did not recover in albino rabbits during the 6-week posttreatment monitoring period, and only 9.9 ± 9.8% of the neovascularization remained at the end of 6 weeks. In the pigmented rabbits, the fluorescence leakage partially returned, but the level of leakage decreased over time during the 6-week posttreatment monitoring period, and only 10.8 ± 9.8% of the neovascularization remained at the end of 6 weeks. Histology demonstrated removal of vasculature without damage to the surrounding neurosensory retina. CONCLUSIONS: These results demonstrate that PUT could precisely remove RNV without damage to the surrounding neurosensory retina in both rabbit strains.

Retinal safety evaluation of photoacoustic microscopy.

Photoacoustic microscopy (PAM) has significant potential as a promising diagnostic method for eye diseases and can provide anatomic and functional information of the retinal and choroidal vasculature. However, there are no FDA-approved PAM systems for ophthalmic imaging. In this study, a comprehensive safety evaluation was performed to evaluate the safety of PAM retinal imaging and whether PAM causes damage to retinal structure or function in rabbit eyes. 12 Dutch-Belted pigmented rabbits received photoacoustic imaging to 57% of the retinal surface area with a laser energy of 5% of the ANSI safety limit for five consecutive days and followed before imaging and 3 days, 1, 2, 3, and 4 weeks post imaging. Retinal morphologic analyses using slit lamp examination, fundus photography, red free, FA, FAF, ICGA, and OCT showed no retinal hemorrhage, edema, detachment, vascular abnormalities, or pigmentary abnormalities in the retina or choroid after PAM imaging. Full-field ERG analysis showed no significant difference in scotopic or photopic a- and b-wave amplitudes or implicit times between the control and experimental eyes over time (n = 6, P values > 0.05). Retinal ultrastructural evaluation using TEM showed normal structure of organelles and nuclei, and no significant loss of cells after PAM. TUNEL assay showed no evidence of cells apoptosis in retina. Retinal histopathology indicated that the architecture and thickness of the retinal layers was well preserved in all experimental eyes. A positive control at 500% of the ANSI limit demonstrated significant damage. The comprehensive retinal safety evaluation demonstrated no damage to retinal structure or function for 4 weeks after PAM imaging in rabbits.

Long-term multimodal imaging characterization of persistent retinal neovascularization using DL-alpha-aminoadipic acid in pigmented and white rabbits.

PURPOSE: Intravitreal (IVT) injection of DL-alpha-aminoadipic acid (AAA) is a new animal model for retinal neovascularization (RNV) reported in rabbits. This study performs longitudinal multimodal imaging for up to 1 year to evaluate DL-AAA RNV in both New Zealand white (NZW) rabbits and Dutch-Belted pigmented (DBP) rabbits. METHOD: Detailed characterization and quantification of this model were performed in these two strains in 32 eyes by optical coherence tomography (OCT), fundus photography, and fluorescein angiography (FA) for up to 16 weeks following DL-AAA administration in 32 eyes and up to 52 weeks in 5 eyes. H & E histology was also performed in these two strains 8 weeks after injection of DL-AAA. RESULT: RNV was successfully generated using 50 µL 80 mM DL-AAA solution for DBP rabbits and 80 µL 80 mM DL-AAA for NZW rabbits. The incidence of persistent vascular leakage is 100% (15/15) for DBP rabbits and 70.6% (12/17) for NZW rabbits at 16 weeks. Complications with NZW rabbits ultimately decreased the efficiency in NZW rabbits to 58.8% (10/17) of NZW rabbits getting persistent (to 16 weeks) vascular leakage without ocular complications as compared with 100% (15/15) in DBP rabbits. Five eyes (2 DBP and 3 NZW) were selected from those demonstrating RNV at 16 weeks and were monitored for up to 52 weeks. All 5 demonstrated persistent RNV to 52 weeks. Quantification of the mean leakage area (MLA) in DBP rabbits is more accurate than in NZW rabbits since the reduced contrast between the leakage and background in NZW rabbits makes it more challenging to quantify. CONCLUSION: DL-AAA can induce persistent and quantifiable RNV in both DBP and NZW rabbits. DBP rabbits have a higher success rate, lower required volume of DL-AAA, and more accurate method for quantification that could be more desirable.

Laser Therapy in the Treatment of Diabetic Retinopathy and Diabetic Macular Edema.

PURPOSE OF REVIEW: This review highlights indications and evidence on laser therapy in the management of diabetic retinopathy and diabetic macular edema. Particular focus is placed upon the benefits and limitations of conventional laser photocoagulation versus more modern laser photocoagulation techniques, as well as the role of laser photocoagulation in treatment of diabetic retinopathy and diabetic macular edema with the frequent utilization of pharmacologic, including anti-vascular endothelial growth factor (VEGF), therapy. RECENT FINDINGS: Laser photocoagulation remains the gold-standard therapy for the effective, definitive treatment of PDR, and also is highly effective in the management of DME. However, numerous recent studies have demonstrated the clinical efficacy and improved functional and anatomic outcomes of combination therapy with pharmacologic treatment. Continuing innovations in laser technology and improved understanding of laser-retinal interactions and pathophysiology demonstrate that laser therapy will continue to play a critical role in the treatment of diabetic retinopathy and diabetic macular edema for many years to come.

Removing Subcutaneous Microvessels Using Photo-Mediated Ultrasound Therapy.

BACKGROUND AND OBJECTIVES: We have developed a novel anti-vascular technique, termed photo-mediated ultrasound therapy (PUT), which utilizes nanosecond duration laser pulses synchronized with ultrasound bursts to remove the microvasculature through cavitation. The objective of the current study is to explore the potential of PUT in removing subcutaneous microvessels. STUDY DESIGN/MATERIALS AND METHODS: The auricular blood vessels of two New Zealand white rabbits were treated by PUT with a peak negative ultrasound pressure of 0.45 MPa at 0.5 MHz, and a laser fluence of 0.056 J/cm2 at 1064 nm for 10 minutes. Blood perfusion in the treated area was measured by a commercial laser speckle imaging (LSI) system before and immediately after treatment, as well as at 1 hour, 3 days, 2 weeks, and 4 weeks post-treatment. Perfusion rates of 38 individual vessels from four rabbit ears were tracked during this time period for longitudinal assessment. RESULTS: The measured perfusion rates of the vessels in the treated areas, as quantified by the relative change in perfusion rate, showed a statistically significant decrease for all time points post-treatment (P < 0.001). The mean decrease in perfusion is 50.79% immediately after treatment and is 32.14% at 4 weeks post-treatment. Immediately after treatment, the perfusion rate decreased rapidly. Following this, there was a partial recovery in perfusion rate up to 3 days post-treatment, followed by a plateau in the perfusion from 3 days to 4 weeks. CONCLUSIONS: This study demonstrated that a single PUT treatment could significantly reduce blood perfusion by 32.14% in the skin for up to 4 weeks. With unique advantages such as low laser fluence as compared with photothermolysis and agent-free treatment as compared with photodynamic therapy, PUT holds the potential to be developed into a new tool for the treatment of cutaneous vascular lesions. Lasers Surg. Med. © 2020 Wiley Periodicals, LLC.

High Resolution Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Visualization of Choroidal Vascular Occlusion.

Photoacoustic microscopy is a novel, non-ionizing, non-invasive imaging technology that evaluates tissue absorption of short-pulsed light through the sound waves emitted by the tissue and has numerous biomedical applications. In this study, a custom-built multimodal imaging system, including photoacoustic microscopy (PAM) and optical coherence tomography (OCT), has been developed to evaluate choroidal vascular occlusion (CVO). CVO was performed on three living rabbits using laser photocoagulation. Longitudinal imaging of CVO was obtained using multiple imaging tools such as color fundus photography, fluorescein angiography, indocyanine green angiography (ICGA), OCT, and PAM. PAM images were acquired at different wavelengths, ranging from 532 to 700 nm. The results demonstrate that the CVO was clearly observed on PAM in both two dimensions (2D) and 3D with high resolution longitudinally over 28 days. In addition, the location and margin of the CVO were distinguished from the surrounding choroidal vasculature after the injection of ICG contrast agent. PAM imaging was achieved using a laser energy of approximately 80 nJ, which is about half of the American National Standards Institute safety limit. The proposed imaging technique may provide a potential tool for the evaluation of different chorioretinal vascular disease pathogeneses and other biological studies.

Real-time photoacoustic sensing for photo-mediated ultrasound therapy.

Photo-mediated ultrasound therapy (PUT) is a novel, noninvasive antimicrovascular approach that can treat neovascularization with high precision. We developed a photoacoustic (PA) sensing (PAS) system for PUT and achieved real-time PAS-guided PUT. Experiments performed on a chicken yolk sac membrane model demonstrated that PAS could monitor the treatment effect in a microvessel during PUT. Vessel shrinkage induced a decrease in the PA signal amplitude, while vessel rupture induced an abrupt increase in the PA signal amplitude. The integrated PUT and PAS system can significantly improve the safety and effectiveness of PUT, and may assist with clinical translation of this novel antimicrovascular technique.

Real-time OCT guidance and multimodal imaging monitoring of subretinal injection induced choroidal neovascularization in rabbit eyes.

Choroidal neovascularization (CNV) is a major cause of vision loss that consists of abnormal growth of new blood vessels from the choroidal vasculature. High resolution in vivo imaging of animal models is essential to better elucidate and conduct research on CNV. This study evaluates a novel multimodal imaging platform combining optical coherence tomography (OCT) and photoacoustic microscopy (PAM). Using real-time OCT guidance subretinal injection to induce and multimodality imaging system to monitor CNV over time in rabbit eyes. The significance of our work lies in providing the optimal setting and conditions to make use of the OCT image guided system to improve the consistency and reproducibility of experimental results in subretinal injection induced CNV model in rabbits. For the first time, this study successfully demonstrated the dual-modality PAM-OCT system, without using exogenous contrast agents, can detect and visualize CNV in the rabbit eye with high resolution. This is promising system for diagnosing and monitoring CNV.

Smartphone-based fundus photography for screening of plus-disease retinopathy of prematurity.

BACKGROUND: Inadequate screening of treatment-warranted retinopathy of prematurity (ROP) can lead to devastating visual outcomes. Especially in resource-poor communities, the use of an affordable, portable, and easy to use smartphone-based non-contact fundus photography device may prove useful for screening for high-risk ROP. This study evaluates the feasibility of screening for high-risk ROP using a novel smartphone-based fundus photography device, RetinaScope. METHODS: Retinal images were obtained using RetinaScope on a cohort of prematurely born infants during routine examinations for ROP. Images were reviewed by two masked graders who determined the image quality, the presence or absence of plus disease, and whether there was retinopathy that met predefined criteria for referral. The agreement between image-based assessments was compared to the gold standard indirect ophthalmoscopic assessment. RESULTS: Fifty-four eyes of 27 infants were included. A wide-field fundus photograph was obtained using RetinaScope. Image quality was acceptable or excellent in 98% and 95% of cases. There was substantial agreement between the gold standard and photographic assessment of presence or absence of plus disease (Cohen's κ = 0.85). Intergrader agreement on the presence of any retinopathy in photographs was also high (κ = 0.92). CONCLUSIONS: RetinaScope can capture digital retinal photographs of prematurely born infants with good image quality for grading of plus disease.

Noninvasive chorioretinal imaging in living rabbits using integrated photoacoustic microscopy and optical coherence tomography.

Most reported photoacoustic ocular imaging work to date uses small animals, such as mice and rats, the eyeball sizes of which are less than one-third of those of humans, posing challenges for clinical translation. Here we developed a novel integrated photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system for dual-modality chorioretinal imaging of larger animals, such as rabbits. The system has quantified lateral resolutions of 4.1 µm (PAM) and 3.8 µm (OCT), and axial resolutions of 37.0 µm (PAM) and 4.0 µm (OCT) at the focal plane of the objective. Experimental results in living rabbits demonstrate that the PAM can noninvasively visualize individual depth-resolved retinal and choroidal vessels using a laser exposure dose of ~80 nJ below the American National Standards Institute (ANSI) safety limit 160 nJ at 570 nm; and the OCT can finely distinguish different retinal layers, the choroid, and the sclera. This reported work may be a major step forward in clinical translation of the technology.

Visual function quality of life measure changes upon conversion to neovascular age-related macular degeneration in second eyes.

PURPOSE: To determine changes in quality of life measures when choroidal neovascularization (CNV) developed in the second eye of patients with initially unilateral neovascular age-related macular degeneration (AMD). METHODS: We analyzed responses to the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ), 36-item Short Form Health Survey (SF-36), and Hospital Anxiety and Depression Scale (HADS) at baseline, and prior to and following second eye CNV diagnosis in 92 participants enrolled in two Submacular Surgery Trials. Paired t-tests for sample sizes over 30 and Wilcoxon signed-rank tests for sample sizes <30 were performed to compare scores. RESULTS: CNV development resulted in statistically and clinically significant changes in responses to 20 of 39 NEI-VFQ items, indicating visual function decline during a mean interval of 25 months. Little difference was noted between baseline scores and prior to CNV diagnosis, which averaged 8.9 months duration. Subscales demonstrated a statistically significant decline in general vision, near activities, distance activities, social functioning, role difficulties, dependency, and driving. There were minimal changes in the HADS and SF-36 scales. CONCLUSION: CNV development in the second eye had a dramatic effect on visual functioning based on patient responses to the NEI-VFQ questionnaire. Our investigation is believed to be the first study using data collected prospectively to demonstrate vision-related quality of life changes that resulted from development of CNV in AMD patients.

Effect of oral niacin on central retinal vein occlusion.

PURPOSE: Niacin, a treatment for dyslipidemia, is known to induce vasodilation as a secondary effect. Previous instances of patients with chronic central retinal vein occlusion (CRVO) and cystoid macular edema (CME) have been observed to spontaneously improve when placed on systemic niacin for hypercholesterolemia. The purpose of this study was to evaluate the effects of niacin on CRVO and associated ocular complications. METHODS: A prospective, single-center, non-randomized, interventional case series of niacin for CRVO was conducted. Best-correct visual acuity (BCVA), central macular thickness (CMT), and ocular complications were analyzed in 50 patients over 1 year. Eight patients were controls. RESULTS: The mean initial logMAR BCVA was 0.915, and improved with niacin to 0.745 (P = 0.12), 0.665 (P = 0.02) and 0.658 (P = 0.03) after 3, 6, and 12 months of follow-up, respectively. At baseline, mean CMT was 678.9 µm, and improved to 478.1 µm (P = 0.001), 388.6 µm (P < 0.001), and 317.4 µm (P < 0.001) for the same time points. The control group had a mean initial logMAR BCVA of 1.023, which gradually deteriorated to 1.162 (P = 0.36) after 12 months, and baseline CMT of 700.0 µm at baseline, which gradually improved to 490.9 µm (P = 0.06) after 12 months. Panretinal photocoagulation for neovascularization was required in 5 patients (13.2%) receiving niacin and 3 (37.5%) controls. CONCLUSIONS: These data suggest that niacin may be associated with functional and anatomic improvements in eyes with CRVO. Future investigations will help ascertain whether there is a role for niacin as an adjunct therapy to intravitreal injections in the management of CRVO.

Anti-angiogenic Therapy for Retinal Disease.

Recent breakthroughs in our understanding of the molecular pathophysiology of retinal vascular disease have allowed us to specifically target pathological angiogenesis while minimizing damage to the neurosensory retina. This is perhaps best exemplified by the development of therapies targeting the potent angiogenic growth factor and vascular permeability mediator, vascular endothelial growth factor (VEGF). Anti-VEGF therapies, initially introduced for the treatment of choroidal neovascularization in patients with age-related macular degeneration, have also had a dramatic impact on the management of retinal vascular disease and are currently an indispensable component for the treatment of macular edema in patients with diabetic eye disease and retinal vein occlusions. Emerging evidence supports expanding the use of therapies targeting VEGF for the treatment of retinal neovascularization in patients with diabetic retinopathy and retinopathy of prematurity. However, VEGF is among a growing list of angiogenic and vascular hyperpermeability factors that promote retinal vascular disease. Many of these mediators are expressed in response to stabilization of a single family of transcription factors, the hypoxia-inducible factors (HIFs), that regulate the expression of these angiogenic stimulators. Here we review the basic principles driving pathological angiogenesis and discuss the current state of retinal anti-angiogenic pharmacotherapy as well as future directions.

PROSPECTIVE TRIAL OF ENDOGENOUS FUNGAL ENDOPHTHALMITIS AND CHORIORETINITIS RATES, CLINICAL COURSE, AND OUTCOMES IN PATIENTS WITH FUNGEMIA.

PURPOSE: Former studies have found rates of endogenous endophthalmitis ranging from 0% to 37% in patients with fungemia. This study sought to prospectively determine the rate and risk factors for endogenous chorioretinitis and endophthalmitis in patients with fungemia. METHODS: A prospective cohort study was performed of consecutive adult inpatients at a single site from 2010 to 2013 of patients with positive blood cultures for fungus. One hundred and nineteen pieces of information were gathered for each patient. RESULTS: A total of 125 patients were enrolled in the study with 7 positive cases of chorioretinitis for a rate of 5.6%. Of these positive cases, 2 patients had endophthalmitis for a rate of 1.6%. Two patients who had a negative initial examination subsequently had a positive examination; 57% of the chorioretinitis patients who could report symptoms were asymptomatic, 57% of the chorioretinitis patients died, and 32% of negative cases died. Prolonged hospitalization, altered mental status, total parenteral nutrition, and gastrointestinal surgery were protective on univariate but not multivariate analysis. CONCLUSION: Despite modern antifungal therapy, fungal chorioretinitis and endophthalmitis continue to occur in patients with positive fungal cultures. Two dilated ophthalmic examinations should still be considered even in asymptomatic patients with fungemia.

Restoration of retinal structure and function after selective photocoagulation.

CNS neurons change their connectivity to accommodate a changing environment, form memories, or respond to injury. Plasticity in the adult mammalian retina after injury or disease was thought to be limited to restructuring resulting in abnormal retinal anatomy and function. Here we report that neurons in the mammalian retina change their connectivity and restore normal retinal anatomy and function after injury. Patches of photoreceptors in the rabbit retina were destroyed by selective laser photocoagulation, leaving retinal inner neurons (bipolar, amacrine, horizontal, ganglion cells) intact. Photoreceptors located outside of the damaged zone migrated to make new functional connections with deafferented bipolar cells located inside the lesion. The new connections restored ON and OFF responses in deafferented ganglion cells. This finding extends the previously perceived limits of restorative plasticity in the adult retina and allows for new approaches to retinal laser therapy free of current detrimental side effects such as scotomata and scarring.