Inflammatory responses after vitrectomy with vitreous substitutes in a rabbit model.

PURPOSE: To investigate the inflammatory response of current and future potential vitreous substitutes in an experimental in vivo vitrectomy model. METHODS: Twenty-five gauge pars plana vitrectomy was performed in the right eye of 60 pigmented rabbits, with subsequent injection of 0.5-1.0 ml of Healaflow® (cross-linked hyaluronic acid, n = 12), Bio-Alcamid® (polyalkylimide, n = 8), silicone oil (n = 12), or balanced saline solution (BSS, n = 28). Postoperative clinical evaluation was performed; and the rabbits were sacrificed at 1 day, 1 week, or 1 month. The eyecups were then examined macroscopically; the retinas sectioned and stained with hematoxylin and eosin (Htx), and immunohistochemically labeled for glial fibrillary acidic protein (GFAP), CD45, galectin-3, CD68, and CD20. Unoperated left eyes from treated animals as well as eyes from untreated animals were used as controls. RESULTS: Vitrectomy without major complications was achieved in 46/60 eyes. The remaining 14 eyes were analyzed separately. One eye developed endophthalmitis after 1 week and was excluded. Eyes treated with Healaflow®, silicone oil, and BSS had a comparable appearance macroscopically and in Htx-stained sections, whereas Bio-Alcamid®-injected eyes exhibited increased macroscopic inflammation and severely affected retinas. GFAP upregulation was present in all treatment groups, most prominent in eyes treated with Bio-Alcamid® and silicone oil. Upregulation of CD45 and CD68 in the inner retina and vitreous space was most prominent with Bio-Alcamid® treatment, and these eyes together with their silicone oil-treated counterparts also displayed a stronger upregulation of CD20-labeled cells compared with remaining groups. General upregulation of galectin-3, mainly in the inner retina, was found in all groups. In eyes with perioperative complications, labeling of CD45, CD68, and especially GFAP was comparably high. CONCLUSIONS: We here describe differences in the postsurgery inflammatory profiles of existing and potential vitreous substitutes. Bio-Alcamid® and silicone oil display severe signs of gliosis and inflammation, whereas Healaflow® elicits minimal reactions comparable with BSS, highlighting its potential application as a vitreous substitute in a future clinical setting.

Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care.

BACKGROUND: Bacteria in the conjunctiva present a potential risk of vitreous cavity infection during 23-gauge pars plana vitrectomy (PPV). Current preoperative procedures used in Sweden include irrigation with chlorhexidine solution (CHX) 0.05% only and no iodine solutions. We evaluated the bacterial diversity and load before and after this single antibacterial measure. METHODS: In a prospective, consecutive cohort we investigated bacterial growth in samples from 40 eyes in 39 consecutive individuals subjected to vitrectomy. A conjunctival specimen was collected from each preoperative patient before and after irrigating of eye with CHX, 0.05% solution. Iodine was not used during any part of the surgery. One drop of chloramphenicol was administered prior to surgery. Samples from vitreous cavity were collected at the beginning and end of vitrectomy. All conjunctival specimens were cultured for different species and quantified using colony forming units (CFU). RESULTS: There was a significant 82% reduction in the total number of CFUs for all bacteria in all eyes (P < 0.0001), and 90% reduction for coagulase negative staphylococci (CoNS) alone (P = 0.0002). The number of eyes with positive bacterial growth in conjunctival samples decreased from 33 to 18 after irrigation with CHX (P = 0.0023). The most common bacteria prior to surgery were CoNS (70%), Propionibacterium acnes (55%) and Corynebacterium species (36%). No case of post-vitrectomy endophthalmitis was reported during mean follow-up time, which was 4.6 ± 2.3 (range; 1.5 to 9) months. CONCLUSIONS: Patients undergoing PPV harbored bacteria in conjunctiva capable of causing post-vitrectomy endophthalmitis. Preoperative preparation with CHX significantly reduced the bacterial load in the conjunctival samples subsequently leading to very low inoculation rates in recovered vitreous samples. Thus, CHX used as a single disinfectant agent might be an effective preoperative procedure for eye surgery in Sweden. This is a relatively small study but the results could be a reference for other intraocular surgeries.

A cross-linked hyaluronic acid hydrogel (Healaflow(®)) as a novel vitreous substitute.

PURPOSE: Vitrectomy requires the substitution of the natural vitreous, as well as tamponading of retinal breaks. Clinically available alternatives such as gas and silicone oil have side effects such as inflammation, secondary glaucoma, cataract, and a need for head posturing. In this study, a hydrogel of cross-linked sodium hyaluronic acid (Healaflow(®)) is evaluated for use as a novel vitreous substitute. METHODS: A combined 25-20-gauge pars plana vitrectomy with posterior vitreous detachment was performed in the right eye of twelve pigmented rabbits, with subsequent injection of approximately 1 ml Healaflow(®). Clinical evaluation, measurement of intraocular pressure (IOP), and full-field ERG were performed postoperatively. The rabbits were sacrificed at different time-points between 42 and 105 days. After enucleation, the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy and immunohistochemistry. RESULTS: Healaflow(®) was successfully used with standard surgical procedures and remained translucent but did lose most of its viscosity during the postoperative period. One rabbit was lost due to unrelated causes. In two eyes iatrogenic partial retinal detachments were seen, and in two eyes significant cataract developed due to intra-operative complications. ERG-recordings revealed no toxic effect on rod or cone function. Routine microscopy and immunohistochemistry demonstrated normal morphology with some Müller cell activation (up-regulation of glial acidic fibrillary protein, GFAP) compared to unoperated eyes and no significant DNA-fragmentation (TUNEL-assay). CONCLUSIONS: Healaflow® did not affect retinal morphology or function negatively during long-term use as a vitreous substitute, making it highly interesting in this setting. An estimated retention time of a few weeks suggests potential for use as a short-term tamponade. Future work will include an increased ratio of cross-linking to prolong the structural integrity of the gel.

A new model for in vitro testing of vitreous substitute candidates.

PURPOSE: To describe a new model for in vitro assessment of novel vitreous substitute candidates. METHODS: The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid®), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow®). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL. RESULTS: Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid®-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow®-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow® and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid®-exposed retinas showed sparse labeling of GFAP. CONCLUSIONS: Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid® had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow® shows protection from culture-induced trauma indicating favorable biocompatibility.

DMEK Surgery at a Tertiary Hospital in Sweden. Results and Complication Risks.

Purpose: This study reports clinical outcomes up to 6 years after Descemet's membrane endothelial keratoplasty (DMEK) performed at the Department of Ophthalmology, Örebro University Hospital, Örebro, Sweden. Methods: The study has a cross-sectional and case series design. Inclusion criteria were all DMEK-operated eyes during 2013-2018 until repeat keratoplasty. Results: Altogether 162 eyes from 120 patients were enrolled. Among eyes without preoperative comorbidities, examined 1-6 years after DMEK, 85.8% achieved visual acuity of 0.1 logMAR or better. The median endothelial cell density (ECD) loss was 27% in a cohort of eyes examined 1-2 years post-DMEK, 31% at 2-3 years, 42% at 3-4 years, and > 60% at 4-6 years post-DMEK. ECD at the examination timepoint was correlated with donor ECD (as expected) and time since surgery. Conclusion: The results from DMEK surgeries in Örebro, Sweden, are promising. Further studies with even longer follow-up are needed to evaluate graft sustainability.

Comparison of UVA- and UVA/riboflavin-induced growth inhibition of Acanthamoeba castellanii.

PURPOSE: To investigate whether ultraviolet light (UVA) at 365 nm can inhibit/eliminate Acanthamoeba growth and if riboflavin would potentiate such an association. METHODS: Acanthamoeba castellanii in a fluid medium with a concentration of approximately 1.7 × 10(4) protozoa/ml were prepared with (0.01 %) and without riboflavin. Exposure of UVA (dose 5.475 J/cm(2)) took place twice, with each illumination period followed by culturing of 10 µl in peptone yeast-extract glucose (PYG) medium for 7 days. Every suspension prepared had a non-exposed control solution. Determination of Acanthamoeba was conducted daily, by count in Burker chamber days 4 through 7 after exposure. Statistical analysis was done by repeated-measurement ANOVA and post-hoc analysis for unpaired samples. RESULTS: The exposure of ultraviolet light resulted in an inhibited growth of Acanthamoeba compared to the non-exposed solutions, with a statistically significant reduction over time (p = 0.0003). The addition of riboflavin did not amplify the effect, and there were no tendencies for an interaction effect between UVA and riboflavin. CONCLUSIONS: The antiprotozoal effect of the UVA wavelength, utilized in CXL, is solely mediated by ultraviolet light, and riboflavin does not seem to amplify the antimicrobial efficacy.

International Olympic Committee (IOC) consensus paper on sports-related ophthalmology issues in elite sports.

Vision plays an important role in an athletes' success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity. The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions. The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue.

UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study.

BACKGROUND: The aim of this work as to investigate the photochemical interaction used in corneal crosslinking (CXL) as the primary therapy for bacterial keratitis. METHODS: A prospective non-randomized study was conducted including 16 patients with a clinical diagnosis of bacterial keratitis. No patient had any prior antibiotic treatment for the current infection. Photography and microbial culturing of the infected cornea were performed. Riboflavin was topically administered for 20 min and ultraviolet light (UVA) exposure settings for treatment of keratoconus were used. After the procedure, clinical examinations were done at least once daily until signs of improvement had been established. The frequency of examinations was thereafter reduced. Antibiotic therapy was initiated if infectious progression was suspected. The trial was registered at ISCRTN.org (no: 21432643). RESULTS: All eyes responded to the photochemical treatment with improvement in symptoms and signs of reduced inflammation. Epithelial healing was achieved in all cases. Antibiotic administration was necessary in two cases. One patient required a human amniotic membrane transplant. CONCLUSIONS: This trial illustrates that photosensitization of riboflavin using UVA at 365 nm has the potential to induce healing in patients with microbial keratitis. The results from the treatment of these 16 patients with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a controlled study in order to assess its efficacy and safety compared to antibiotics.

Retinal surgery quality indicators for uncomplicated primary rhegmatogenous retinal detachment without a national registry.

PURPOSE: The objective of this study was to evaluate the possibility of analysing quality indicators for uncomplicated primary rhegmatogenous retinal detachment in a hospital department of ophthalmology without the support of a national registry or need to collect data from referring ophthalmological centres. METHODS: In 2014, we operated 231 consecutive eyes with uncomplicated retinal detachment. Our quality indicators were primary anatomical success, final anatomical success and postoperative endophthalmitis. We reviewed medical records in our university surgical department retrospectively and compared them with medical records from the regional hospitals that had referred most of the operated patients and done their own postoperative examination. Our hypothesis was that any retinal re-detachment and/or serious postoperative complication would be reported back. RESULTS: The medical records at the surgical department revealed primary anatomic success for 91.3% of eyes and final anatomical success of 99.6%. The data from the regional hospitals confirmed that our hypothesis was correct. All patients with adverse outcomes were referred back for reoperation. Patients who were not referred again had an attached retina and showed no signs of endophthalmitis. CONCLUSION: Our hypothesis that data in the surgical department's medical records would closely reflect those in referring hospitals was borne out. This supports, under current conditions, an effective strategy for analysing chosen quality indicators without relying on a national registry or reviewing records from regional hospitals.

Experimental vitreous tamponade using polyalkylimide hydrogel.

PURPOSE: To evaluate polyalkylimide as a possible vitreous tamponading agent. METHODS: A 20-gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of six pigmented rabbits. Approximately 1 ml of viscoelastic gel, polyalkylimide (Bio-Alcamid) was thereafter injected into the vitreous space. Full-field ERG and intraocular pressure (IOP, Tonopen) was measured pre-and postoperatively at regular intervals up to 28 days. At day 6 or 28, the rabbits were sacrificed and the eyes were examined macroscopically, photographed, and prepared for histological examination with routine microscopy. RESULTS: The viscoelastic hydrogel was successfully injected, and remained translucent with preserved gel properties throughout the postoperative period. The postoperative IOP was unchanged compared to preoperative values. Five of six eyes displayed retinal edema or pigmentary changes centrally while the periphery appeared intact. ERG recordings showed a radical decrease in rod- and cone-derived B-wave amplitudes. Histological examination confirmed varying degrees of edema combined with neuronal cell death within the retinal layers in the central part of the fundus, while the peripheral part appeared intact. CONCLUSION: Polyalkylimide displays favourable physical properties when used as a vitreous tamponade. However, the hydrogel causes functional and morphological retinal damage when in direct contact with the inner retina. Possible pathological mechanisms include osmotic imbalance and direct toxic effects, and modification of biochemical properties is warranted before clinical use will be possible.

A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades.

Purpose: To develop a treatment model of rhegmatogenous retinal detachment (RRD) in which the effects of various vitreous tamponades can be explored. Methods: In a primary session, detachment was produced in the right eye of 24 rabbits using vitrectomy, posterior vitreous detachment, retinal break induction, and subretinal injection of viscoelastic solution. The following day, detachments were treated in 16 eyes using SF6 (n = 8) or Healaflow® (HF, a cross-linked hyaluronic acid hydrogel, n = 8) tamponade. Animals were followed for 1 month and thereafter examined macroscopically and morphologically in hematoxylin and eosin-stained sections. Results: Retinal detachment (RD) was successfully treated using repeated surgery. Two HF eyes developed progressive vitritis and were excluded from further evaluation. Enlargement of the initial retinal rupture with concomitant RD was seen in 4/8 SF6 eyes, while all 6 HF eyes displayed an attached retina. Attached areas showed a normal retinal morphology except for in 1 HF eye with extensive degeneration. Conclusions: The RRD repeat vitrectomy model offers a possibility to explore the efficacy and complications of novel potential vitreous tamponades. Gel-based Healaflow® displays excellent anatomic reattachment, however, vitritis and retinal degeneration in some cases warrants further investigation.

Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA).

BACKGROUND: To evaluate the antibacterial efficacy of photo-activated riboflavin using Ultraviolet A (UVA) on three bacterial strains commonly detected in keratitis. METHODS: Three bacterial strains (Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa) were cultured on blood/hematin-agar plates and dispersed in PBS. Dispersion was done of 10 microl of bacterial stock-solutions in 90 microl of RPMI, where different riboflavin molarities had been added, to achieve a bacterial concentration of 1-4 x 10 (4)/ml. Riboflavin end molarities before illumination were 0, 100, 200, 300 and 400 microM. Each solution had a negative control. The solutions were illuminated with UVA (365 nm) for 30 minutes (5.4 J/cm(2)) and then continued for a total time of 60 minutes (10.8 J/cm(2)). A count of CFU was conducted after incubation and results compared. RESULTS: In all tested strains, a slight decrease of bacteria was seen when exposed to UV for 30 minutes. A doubling of the UV dose showed a marked decrease of bacterial count in all bacteria tested. The combination of UV and riboflavin showed a more extensive reduction of CFU, confirming an interaction effect between UV and riboflavin. CONCLUSION: Riboflavin photo-activation using UVA (365 nm) can achieve an extensive eradication of bacteria, and the combination is more potent in reducing bacterial number than UV alone.

Electroporation therapy of skin cancer in the head and neck area.

BACKGROUND: Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent. OBJECTIVE: To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin. MATERIALS AND METHODS: Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow-up period was 24 months and included biopsies after 8 weeks. RESULTS: In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow-up period CONCLUSION: Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer.

A prospective long-term follow-up study of optic disc pit maculopathy treated with pars plana vitrectomy, drainage of subretinal fluid and peeling of internal limiting membrane.

PURPOSE: To describe the long-term results of surgical repair of patients with optic disc pit maculopathy (ODP-M). METHODS: Prospective, consecutive, noncomparative follow-up study including 12 patients with ODP-M treated by pars plana vitrectomy (PPV), peeling of internal limiting membrane followed by gas tamponade. Subretinal fluid (SRF) was drained in 11 eyes through a retinotomy without laser photocoagulation. Preoperatively, macular detachment with retinoschisis was seen in 9 out of 12 eyes with three eyes having only subretinal fluid in the macular area. The median age at surgery was 20 years (range 9-60 years). RESULTS: Follow-up time from initial surgery was 63 months (median). Eight eyes were anatomically reattached after one operation without remaining SRF in the macula. Two patients required a reoperation due to leakage from the retinotomy and another two underwent a second PPV procedure due to late recurrences. Successful healing was at follow-up control observed in 11 of 12 eyes. There was no statistically significant difference in visual acuity between patients before and after surgery (p = 0.24). Central visual field defects with depressed mean deviation were detected in all treated eyes. CONCLUSION: In this long-term study of ODP-M final outcome regarding healing was relatively efficacious, however, a relatively large proportion had complications associated to retinotomies. We conclude that drainage of SRF should likely be avoided since it appears to contribute little to the resorption rate of SRF and seems to linked to unnecessary risks.

Levels of beta-trace protein in optic disc pit with macular detachment.

BACKGROUND: To report beta-trace protein (ßTP) levels in the subretinal fluid (SRF) of four patients with a macular detachment associated with optic disc pit (ODP). METHODS: Four patients with a serous retinal detachment involving the macula was operated by pars plana vitrectomy (PPV) with C2 F6 gas tamponade and peeling of internal limiting membrane (ILM). Patients with a follow-up period exceeding one year postoperatively were included in the study. The SRF was drained using a fine cannula without laser photocoagulation, and the samples were analysed using particle-enhancing nephelometry. The levels of ßTP were compared to 20 routine cerebrospinal fluid (CSF) samples. RESULTS: In four of the five samples from SRF had relatively low ßTP levels, with a mean concentration of 6.6 mg/l (range 2.0 to 23.1 mg/l) compared to 16.0 mg/l (range 6.3-26.8 mg/l) in CSF. The only SRF sample within the range corresponding to normal CSF was the first sample from patient 4, and the analysis of the renewed aspirate during the second operation was 2.8 mg/l. Postoperatively, the regression of SRF was slow, but regression of SRF in the foveal region took place in all cases; however, visual acuity (VA) was improved in only half of the patients. CONCLUSION: The results from the analysed SRF regarding ßTP concentration in these patients indicate that the SRF in ODP is not identical to CSF, as the concentrations of ßTP differ.

[Floorball ­ a common cause of sport related eye injury]. / Innebandy är en vanlig orsak till sportrelaterade ögonskador - Skyddsglasögon bör användas vid innebandyspel på alla nivåer.

Floorball - a common cause of sport related eye injury The aim of this study was to survey the incidence and type of sport related to eye injuries with special interest in floorball. A prospective study was conducted December 1st 2013 through November 30th 2014 at the Department of Ophthalmology, Örebro University Hospital. All patients presenting with an acute sports related eye injury were offered to be included. Information was collected from a self-administered questionnaire and from medical journals. During the study period, 49 patients sought care for sports related eye injuries, and 26 (53%) of those were related to floorball. The number of patients who agreed to take part in the study was 38, of which 25 had injuries related to floorball. Among the floorball players, there were two patients where the injury caused permanent vision impairment. None of the floorball players wore eye protection at the time of injury. According to this study, protective eyewear should be recommended when playing floorball, regardless of age or setting.

The efficiency of cross-linking methods in eradication of bacteria is influenced by the riboflavin concentration and the irradiation time of ultraviolet light.

PURPOSE: To determine bacterial eradication using numerous riboflavin concentrations and different ultraviolet light A (UVA) radiant and exposure time in an experimental model. METHODS: Dilutions of Staphylococcus epidermidis were mixed with riboflavin at varying concentrations (0.007­0.09%). Effects on bacterial growth were evaluated after 0, 3, 6, 30 and 60 min of UVA exposure (irradiance 30 and 3 mW/cm2). Standard settings of UVA were compared with high-power UVA approach. Different fluid thicknesses of the exposed dilutions were also examined to improve the model. RESULTS: Bacterial eradication (%) was increased after 60 compared with 30 min of UVA exposure for concentrations of 0.03­0.07% but not for 0.09% riboflavin.There was a significant difference between the efficacy between 0.03 and 0.09% and eradication dropped from 80%to 50%(p = 0.01).A correlation could be calculated for the amount of riboflavin at 60 min of UVA and the ability to kill bacteria(p = 0.01). The antibacterial effect was more pronounced when the tested bacterial suspension thickness was reduced. High-power UVA method was less potent in microbial elimination, eradicating only 60%of bacteria after 6 min versus 97­99%after 60 min in the low-power setting, compared with respective controls (p = 0.02). CONCLUSIONS: In these in vitro experiments, a longer UVA exposure time in combination with lower riboflavin levels were found to be favourable in killing bacteria as compared to the standard cross-linking settings. Further studies are needed to evaluate the clinical relevance of these findings.

Experts do not agree when to treat retinopathy of prematurity based on plus disease.

OBJECTIVES: To investigate inter-reader agreement on five severity levels of central vascular changes (none, mild, moderate, severe pre-plus disease, plus disease) and aggressive posterior retinopathy of prematurity (ROP), and to see whether an unintended shift in indication for treatment occurred. METHODS: Four international ROP readers participated. Before the grading of the photographs, the readers were informed that a high proportion of advanced ROP cases were included. In total, 243 photographs/948 quadrants were available from 136 infants. As a standard series of photographs was available, grading was performed under optimised conditions. RESULTS: The four readers agreed on the quadrant scores of only 70 (7.38%) of the 948 quadrants--that is, on 1, 5, 15, 4 and 45 quadrants for scores 0, 1, 2, 3 and 4, respectively. The mean scores differed systematically between the readers (permutation test, p<0.0001). Agreement on presence of aggressive posterior ROP from all four readers was not obtained for any of the photographs. Readers scored plus disease in at least two quadrants in 95.5% of the eyes for which treatment was indicated. All four readers agreed on the scoring of indication for treatment for 195 eyes (80.2%); however, treatment was only recommended in 18 (7.4%) eyes. One reader was found to differ systematically from the others in indicating treatment (Rasch analysis; p=0.0001). Finally, a significant shift in indication for treatment occurred between birth period 2000-2002 and 2003-2006 (Mann-Whitney rank sum test, p<0.001). CONCLUSIONS: Inter-reader agreement on central vascular changes is poor, especially when based on more than two rating categories. The subjective nature of diagnosing such vascular changes possibly resulted in earlier treatment of preterm infants in Denmark over the entire study period (1997-2006). The recent increased incidence of treated infants in Denmark is, at least in part, explained by a significant shift in indication for treatment.

Vasoproliferative retinal tumours in a Swedish population.

PURPOSE: To describe the clinical appearance and the visual outcome of a cohort of patients with vasoproliferative retinal tumours (VPRTs) that were diagnosed and treated between 2002 and 2007 at the University Hospital of Örebro. METHODS: Nine patients with diagnosed VPRTs were included in a retrospective study. The mean age at the time of diagnosis was 50.2 years (range 7-74 years). Follow-up time ranged between 14 and 83 months (mean 42.6). Nine out of ten eyes received cryotherapy; six eyes were also treated with photocoagulation. One patient was treated with intravitreal injections of ranibizumab (Lucentis(®)) and another was referred for brachytherapy. Because of persisting macular oedema, one eye was treated with intravitreal injection of triamcinolon. RESULTS: Of the treated eyes, one had anterior uveitis, six had macular oedema at baseline and four had an exudative retinal detachment at the time of diagnosis. Seven eyes underwent vitrectomy because of epiretinal membranes. Visual acuity at diagnosis was 0.21 (mean) (range 0.02-0.6) and at latest check-up 0.30 (mean) (range light perception (LP)-1.0), with improvement in six eyes and deterioration in two. Two out of four patients with retinal detachment were successfully treated surgically. CONCLUSION: VPRTs are benign intraretinal changes. Several complications are associated with this condition. All patients in this study had symptom-giving tumours and six patients (six eyes) already had profound macular oedema at presentation. In these cases, when complications have already developed, the final visual prognosis is poor, thereby making it important to detect these tumours early. The patient who received anti-vascular endothelial growth factor (VEGF; Lucentis) therapy showed a slow improvement and distinct regression in exudations during the follow-up time. However, no increase in visual acuity was seen. At latest examination a peripheral exudative retinal detachment was still observed. Whether anti-VEGF treatment is effective, as either an alternative or complementary therapy, must be established in the future.