Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched healthy volunteers.

PURPOSE: Fractal analysis can be used to quantitatively analyze the retinal microvasculature and might be a suitable method to quantify retinal capillary changes in sickle cell disease (SCD) patients. Retinal oximetry measurements might function as a proxy for the pathophysiology of cerebrovascular diseases. Moreover, hypoxia has an important role in the pathophysiology of diabetic and other retinopathies. However, little is known about the oximetry around the macula in SCD patients. With this study, we explored the feasibility to perform these quantified measurements in SCD patients. METHODS: Retinal microvascular and oximetry measurements were performed in eight SCD patients and eight healthy matched controls. Oximetry pictures and non-invasive capillary perfusion maps (nCPM) were obtained by the retinal function imager. Measurements were conducted twice on two different study days. Measured variables included monofractal dimension (Dbox), relative saturation, deoxygenated hemoglobin (deoxyHb), and oxygenated hemoglobin (oxyHb) concentration. RESULTS: No statistically significant differences in vessel density were found in the different annular zones (large vessels, p = 0.66; small vessels, p = 0.66) and anatomical quadrants (large vessels, p = 0.74; small vessels, p = 0.72). Furthermore, no significant between-group differences were found in the other different anatomical quadrants and annular zones around the fovea for relative saturation levels and deoxygenated Hb. However, the oxyHb levels were significantly lower in SCD patients, compared with those in matched controls in the temporal quadrants (p = 0.04; p = 0.02) and the superior nasal quadrant (p = 0.05). CONCLUSIONS: Our study demonstrated the feasibility of multispectral imaging to measure retinal changes in oxygenation in both SCD patients and matched volunteers. The results suggest that in SCD patients before any structural microvascular changes in the central retina are present, functional abnormalities can be observed with abnormal oximetry measurements.

Correction to: Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched healthy volunteers.

In the published online PDF version, Figure 3 was incorrectly captured the same as Figure 1.

Numerical study of the effect of head and eye movement on progression of retinal detachment.

Rhegmatogenous retinal detachment (RD) is a sight threatening condition. In this type of RD a break in the retina allows retrohyaloid fluid to enter the subretinal space. The prognosis concerning the patients' visual acuity is better if the RD has not progressed to the macula. The patient is given a posturing advice of bed rest and semi-supine positioning (with the RD as low as possible) to allow the utilisation of gravity and immobilisation in preventing progression of the RD. It is, however, unknown what external loads on the eye contribute the most to the progression of a RD. The goal of this exploratory study is to elucidate the role of eye movements caused by head movements and saccades on the progression of an RD. A finite element model is produced and evaluated in this study. The model is based on geometric and material properties reported in the literature. The model shows that a mild head movement and a severe eye movement produce similar traction loads on the retina. This implies that head movements-and not eye movements-are able to cause loads that can trigger and progress an RD. These preliminary results suggest that head movements have a larger effect on the progression of an RD than saccadic eye movements. This study is the first to use numerical analysis to investigate the development and progression of RD and shows promise for future work.

Suspected bacterial endophthalmitis following intravitreal anti-VEGF injection: case series and literature review.

AIM: To report an up-to-date overview of all patients reported in the literature with suspected bacterial endophthalmitis following anti-VEGF injection. Secondly, to identify specific symptoms and signs to differentiate between infectious and noninfectious endophthalmitis. METHODS: A Pubmed search retrieved 12 retrospective case series which had included a total of 118 patients with suspected bacterial endophthalmitis after anti-VEGF injection. Data of 15 patients from the Rotterdam Eye Hospital were added. Patients were divided into three groups: those who did not receive intravitreal antibiotics (group A), patients who received intravitreal antibiotics with biopsy-negative cultures (group B) and those with biopsy-positive cultures (group C). RESULTS: The median time between anti-VEGF injection and presentation with suspected bacterial endophthalmitis was 1 day in group A compared to 3 days in groups B and C. At presentation, patients of group A had a better median visual acuity (logMAR 1.0) compared to those in groups B and C (logMAR 2.1 and 2.5, respectively). CONCLUSION: This study suggests that patients presenting with a visual acuity of 20/200 (logMAR 1.0) or less and later than 24 h after injection are more likely to have bacterial endophthalmitis. To prevent undertreatment in these patients, the threshold to proceed to vitreous biopsy and empirical intravitreous antibiotics should be low.

Hyperfluorescence of the optic disc with indocyanine green angiography.

PURPOSE: One-fourth of the patients with exudative age-related macular degeneration (AMD) treated with an autologous retinal pigment epithelium (RPE)-choroid translocation had a hyperfluorescent optic disc with indocyanine green angiography (ICGA). This study aimed to identify whether indocyanine green (ICG)-assisted surgery was related to the hyperfluorescence of the optic disc with ICGA. METHODS: Retrospective observational case series of 31 AMD patients treated with an RPE-choroid translocation and who had ICGA after surgery. The ICGAs were assessed for hypo/iso/hyperfluorescence of the optic disc and fluorescence was related to the time interval between ICGA and the possible use of intravitreal ICG. RESULTS: The optic disc was hyperfluorescent in six patients, isofluorescent in one, and hypofluorescent in 24 patients. All hyperfluorescent optic discs and 7 of the 24 hypofluorescent optic discs were preceded with ICG-assisted surgery with a time interval of 7+/-3 weeks and 43+/-12 weeks, respectively (P=0.001, Student t-test). The other 17 hypofluorescent discs were not preceded by ICG-assisted surgery and the one isofluorescent optic disc was observed 32 weeks after ICG-assisted surgery. CONCLUSION: There was a statistically significant correlation between intravitreal ICG use during surgery and a hyperfluorescent optic disc with ICGA in our patient group.

Micro-scale thermal tissue gripper.

During eye surgery translocating a graft of retinal tissue without damaging the vulnerable top layer is highly problematic using the currently available instruments. This study presents indirect Heat Induced Attachment and Detachment (HIAD) as a new concept for single side attachment of tissue to, and detachment from a heated metal wire. A small-scale prototype was built, having a 50 mum molybdenum wire that could be heated via an electric current. Tests (n = 60) were performed on submerged chicken meat to study the attachment and detachment properties of the prototype at different electric signal lengths. A 9V signal was applied to the prototype, with amplifier input signal lengths varying from 0.6-1.5 ms. Voltages and currents were sampled at 250 kHz to obtain energies. Both attachment and detachment occurred with 98% and 90% certainty, respectively, supplying 41 and 110 mJ of energy to the prototype in 0.7 and 1.5 ms. The attachment strength was estimated at 0.2 mN. Visible damage appeared to be approximately 0.005 mm(2). The concept of indirect heating of the instrument-tissue interface proved to be effective as the prototype could induce attachment and detachment of tissue. Indirect HIAD may be applicable in many different surgical applications.

Retinal pigment epithelium (RPE)-choroid graft translocation in the treatment of an RPE tear: preliminary results.

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.

[New drugs; pegaptanib and ranibizumab]. / Nieuwe geneesmiddelen; pegaptanib en ranibizumab.

The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized by vascular growth and leakage in the retina. Two new drugs, pegaptanib and ranibizumab, have been shown to improve vision or slow the progression of AMD. Both drugs inhibit the action of vascular endothelial growth factor--pegaptanib as an oligonucleotide and ranibizumab as a monoclonal antibody--thereby decreasing angiogenesis in the eye. Adverse effects are associated with the intravitreal administration of both drugs and include increased intraocular pressure, local bleeding, and infection.

[The Dutch version of the Radner Reading Chart for assessing vision function]. / De Nederlandse versie van de Radner-leeskaart voor het beoordelen van de functionele visus.

A chart for measuring visual acuity is a better functional test than the routine distance visual acuity testing with single optotypes. The characteristics of a good reading chart are: logarithmically diminishing print size, simultaneous measurement of reading acuity and reading speed, and the calculation of one score for reading acuity corrected for the number of reading errors. The original German-language Radner Reading Chart meets all these requirements, and above all emphasizes the principle of 'sentence optotypes' i.e. highly standardized sentences, because sentence complexity also influences reading performance. Sentence optotypes were created in the Dutch language and tested according to Radner's strict principles. The most equally matched sentence optotypes in terms of reading speed and number of reading errors were selected for the introduction and printing of the first Dutch version of the Radner Reading Chart. The Dutch Radner Reading Chart is precise and practical and therefore useful for research and daily practice.

An outbreak of endophthalmitis after extracapsular cataract surgery probably caused by endotoxin contaminated distilled water used to dissolve acetylcholine.

AIM: To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. METHODS: In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. RESULTS: In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non-typeable Pseudomonas spp. CONCLUSIONS: These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time.

A pilot study on the use of a perfluorohexyloctane/silicone oil solution as a heavier than water internal tamponade agent.

AIMS: To report a prospective two centred non-comparative interventional pilot study of a solution of perfluorohexyloctane and silicone oil (Densiron-68) as a heavier than water internal tamponade. METHODS: 42 consecutive patients were recruited. The indications include proliferative vitreoretinopathy, retinal detachments arising from inferior retinal breaks, and inability to posture. RESULTS: The success rate with one operation using Densiron was 81% and with further surgery 93%. At the end of the study all tamponade agents were removed in 90% of patients. Visual acuity improved from mean logMAR of 1.41 (SD 0.64) to 0.94 (SD 0.57), p = 0.001. There was little evidence of dispersion and excessive inflammation. CONCLUSION: This new tamponade agent is being compared to conventional silicone oil in a prospective international randomised trial.

Autologous peripheral retinal pigment epithelium translocation in patients with subfoveal neovascular membranes.

AIM: To evaluate the possibility of translocating autologous peripheral retinal pigment epithelial (RPE) cells and enhance their adhesion to improve functional outcome after choroidal neovascular membrane extraction in patients with subfoveal neovascular membranes. METHODS: A prospective, non-controlled surgical study in eight consecutive patients operated between February and July 2001 with final data monitoring in July 2002. All patients had mixed subfoveal membranes of 2-4 disc diameters. Functional tests included Snellen vision and central fixation testing. During vitrectomy, after the extraction of the neovascular complex, 8 x 10(4)-16 x 10(4) RPE cells were removed from the periphery and translocated under the macula following the submacular injection of 2 microg of poly-L-lysine to promote adhesion of the cells. RESULTS: With a follow up ranging from 3 months to 16 months, a pigmented area was seen in the extraction bed of the neovascular membrane in only one patient. Fixation was at the edge of the extraction bed in three patients. Vision remained the same in five patients and deteriorated in three (all with retinal detachment). Retinal detachment due to proliferative vitreoretinopathy occurred in three patients. CONCLUSIONS: The translocation of autologous peripheral RPE cells after membrane extraction was technically possible in a sterile manner, but was associated with a high proliferative vitreoretinopathy rate and in the present series had no measurable positive effect on functional outcome.

Symptoms predictive for the later development of retinal breaks.

OBJECTIVE: To identify symptoms in patients with isolated posterior vitreous detachment predictive for the later development of retinal breaks. METHODS: Two hundred eighty consecutive patients seen with symptoms of posterior vitreous detachment were prospectively asked to complete a questionnaire detailing their symptoms. At the time of presentation and follow-up, all patients had a full ophthalmologic examination including slitlamp biomicroscopy with Goldmann 3-mirror contact lens after maximal pupil dilatation. Two hundred fifty patients with an isolated posterior vitreous detachment were included and reexamined 6 weeks after the onset of symptoms. If small retinal or vitreous hemorrhages were detected, patients were reexamined after 2 weeks. RESULTS: In 13 patients (5.2%) a retinal break was detected at reexamination. Logistic regression analysis with backward elimination revealed that symptoms of flashes in combination with clouds or multiple (>10) small dots at the time of the initial examination or an increase of floaters after the initial examination were statistically significantly (P<.001) related to the development of new breaks. These symptoms had a predictive value for the presence or absence of a new retinal break of 75.0% and 99.6%, respectively. CONCLUSIONS: Specific symptoms can identify patients at risk for the development of new retinal breaks after an initial examination in which no abnormalities were found and may obviate the need for follow-up appointments of patients not at risk.

Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis.

BACKGROUND/AIMS: To study the intravitreal antibiotic concentrations and the efficacy of an intravitreal dosing regimen to treat patients with postoperative bacterial endophthalmitis. This regimen, based on pharmacokinetic/pharmacodynamic considerations, relies on a repeat antibiotic injection of a lower dose than is generally used. METHODS: In consecutive patients with suspected postoperative endophthalmitis a vitreous biopsy for bacterial culture was taken before 0.2 mg vancomycin and 0.05 mg gentamicin were injected intravitreally. After 3 or 4 days a second biopsy was taken for bacteriological culture and to measure intravitreal vancomycin and gentamicin concentrations, followed by a repeat injection of 0.2 mg vancomycin. RESULTS: 17 patients entered the study. In 11 patients the initial bacterial culture was positive, predominantly coagulase negative staphylococci. All second vitreous biopsies were sterile. Intravitreal vancomycin levels varied between 2.6 and 18.0 microg/ml (mean 10.3 (SD 4.1) microg/ml) after 3 days and between 3.1 and 16.6 microg/ml (mean 7.5 (6.2) microg/ml) after 4 days which is well above the minimal inhibitory concentration for most micro-organisms. Concentrations of intravitreal gentamicin varied between 0.90 and 3.3 microg/ml (mean 1.6 (0.72) microg/ml) after 3 days and between 1.2 and 2.6 microg/ml (mean 1.9 (0.99) microg/ml) after 4 days. CONCLUSION: This dosing regimen resulted both in adequate intravitreal vancomycin and gentamicin levels for over a week as well as in negative second cultures. This study also provides new information on intravitreal vancomycin and gentamicin concentration over time in patients with postoperative endophthalmitis.

Dexamethasone concentration in the subretinal fluid after a subconjunctival injection, a peribulbar injection, or an oral dose.

PURPOSE: To determine dexamethasone concentrations in the subretinal fluid of patients after a peribulbar injection, a subconjunctival injection, or an oral dose of dexamethasone and to compare the results with those of previous similar studies of dexamethasone concentrations in the vitreous. DESIGN: Prospective, nonrandomized, comparative trial. PARTICIPANTS: One hundred forty-eight patients with a rhegmatogenous retinal detachment. METHODS: Fifty patients received a peribulbar injection of 5 mg dexamethasone disodium phosphate, 49 received a subconjunctival injection of 2.5 mg dexamethasone disodium phosphate, and 49 received an oral dose of 7. 5 mg dexamethasone at various time intervals before surgery. At the time of surgery, a subretinal fluid sample was taken from each patient. MAIN OUTCOME MEASURES: The dexamethasone concentration in the subretinal fluid measured by radioimmunoassay. RESULTS: The estimated maximum dexamethasone concentrations in the subretinal fluid after the peribulbar injection, the subconjunctival injection, and the oral dose were, respectively, 82.2 ng/ml (standard error, 17. 6), 359 ng/ml (standard error, 80.2), and 12.3 ng/ml (standard error, 1.61). Corrected for dose, the maximum dexamethasone concentrations after subconjunctival injection and peribulbar injection were, respectively, 120 (95% confidence interval, 54/180) and 13 (95% confidence interval, 6.8/20) times greater than after oral administration. CONCLUSIONS: A subconjunctival injection of dexamethasone disodium phosphate is more effective in delivering dexamethasone into the subretinal fluid of patients with a rhegmatogenous retinal detachment compared with peribulbar injection or oral administration. The subretinal dexamethasone concentrations were higher than concentrations measured in the vitreous in previous studies with a similar setup after all three delivery methods.

Retinal vasculitis occurring with common variable immunodeficiency syndrome.

PURPOSE: To report severe retinal vasculitis causing decreased vision in three patients with the common variable immunodeficiency syndrome. METHOD: Case report. Three patients with common variable immunodeficiency syndrome developed decreased vision secondary to retinal vasculitis. Fluorescein angiography was performed in all three patients. Peribulbar injections were given in one patient, and two patients were treated with oral steroids and cyclosporin. RESULTS: All three patients were young and had classic common variable immunodeficiency syndrome. Bilateral retinal vasculitis and diffuse retinal edema were present in all three patients, and two patients had retinal neovascularization in the absence of ischemia. No evidence of intraocular infection was present, and none was detected systematically. Visual acuity decreased in five of the six eyes and was responsive to treatment in only one patient (both eyes). CONCLUSION: Retinal vasculitis may be another autoimmune manifestation of common variable immunodeficiency syndrome.

Follow-up of functionally lost eyes after vitrectomy and silicone oil tamponade for tractional retinal detachment.

BACKGROUND: Is there any association between, on the one hand, retention or removal of silicone oil or any specific ocular finding in patients with functionally lost eyes after vitrectomy and silicone oil tamponade for tractional retinal detachment and, on the other, a greater chance of preservation of the eye? This information is important in deciding whether to remove silicone oil, as well as in counseling patients about their individual chances of preserving their eye. METHODS: Seventy-three consecutive patients with a functionally lost eye with a minimum follow-up of 3 years were retrospectively studied. The relation between the variables at study entry or the removal of silicone oil during the follow-up period and a subsequent intervention (enucleation, evisceration or conjunctival cover with a scleral shell) were tested for statistical significance with Cox proportional hazards analysis. RESULTS: The absence or removal of silicone oil was not associated with a greater chance of finally preserving the eye. Nor could we identify other factors which predicted better chances of preservation. CONCLUSION: The notion that functionally lost eyes after treatment with vitrectomy and silicone oil tamponade for complicated tractional retinal detachment have better chances of preservation of the eye without silicone oil is not supported by our study.

High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection.

PURPOSE: To determine the dexamethasone concentration in aqueous, vitreous, and serum of patients after a subconjunctival injection with dexamethasone disodium phosphate and to compare the effectiveness of a subconjunctival injection as a method of delivering dexamethasone into the vitreous with that of two previously tested routes: peribulbar injection and oral administration. METHODS: In a prospective study, 50 phakic patients who underwent a pars plana vitrectomy received a single subconjunctival injection with 2.5 mg of dexamethasone disodium phosphate, aqueous solution (after topical anesthesia and a subconjunctival injection with lidocaine) at varied intervals before surgery. An aqueous and a vitreous sample were taken from each patient, and serum samples were collected at multiple time points from nine of 50 patients. Dexamethasone concentrations were measured by radioimmunoassay. RESULTS: The estimated maximum dexamethasone concentration in the aqueous was 858 ng per ml at 2.5 hours after injection, and in the vitreous, 72.5 ng per ml at 3 hours. In serum, a mean maximum concentration of 32.4 ng per ml was measured at approximately 30 minutes after injection. CONCLUSIONS: Subconjunctival injection of 2.5 mg of dexamethasone disodium phosphate resulted in an estimated vitreous dexamethasone peak concentration three and 12 times higher, respectively, than after a peribulbar injection of 5 mg of dexamethasone disodium phosphate and an oral dose of 7.5 mg of dexamethasone. Thus, a subconjunctival injection is the most effective method of delivering dexamethasone into both the anterior and posterior segments of the eye. Systemic drug absorption is considerable and is of the same order of magnitude as after peribulbar injection.