Incidence and long-term outcome of laser pointer maculopathy in children.

PURPOSE: Single center study to evaluate the incidence and long-term outcome of laser pointer maculopathy (LPM). METHODS: Medical records of 909,150 patients visiting our institution between 2007 and 2020 were screened in our electronic patient record system using the keywords "laserpointer," "laser pointer," and "solar." RESULTS: Eight patients (6/2 male/female, 11 eyes) with a history of LPM were identified by fundoscopy and optical coherence tomography (OCT), all of whom were children (6/2 male/female). Mean age at injury was 12.1 years (range 6-16). Five children (62.5%) were injured between 2019 and 2020, three (37.5%) between 2007 and 2018. Median best-corrected visual acuity (BCVA) of affected eyes at first presentation was 20/25 (range 20/50-20/16). Follow-up examination was performed in seven children (10 eyes) with a median follow-up period of 18 months (range 0.5-96). BCVA improved in 4 children (5 eyes; BCVA at follow-up 20/22.5, range 20/40-20/16). Three of these four children were treated with oral steroids. OCT revealed acute signs such as intraretinal fluid to resolve quickly, while outer retinal disruption persisted until the last follow-up in eight of eleven eyes. These lesions resembled lesions of patients with solar retinopathy of which seven cases (11 eyes) were identified between 2007 and 2020. CONCLUSION: Readily available consumer laser pointers can damage the retina and the underlying retinal pigment epithelium, possibly leading to long-lasting visual impairments. The number of laser pointer injuries has increased over the last years. Therefore, access to laser pointers for children should be strictly controlled.

Comparison of two Schwann Cell-Containing Orbital Tumors: Schwannoma and Ganglioneuroma. / Gegenüberstellung zweier Schwann-Zell-haltiger orbitaler Tumoren: Schwannom und Ganglioneurom.

Orbital tumors comprise a variety of diseases, although tumors of the peripheral nerves are rare. Of these, schwannoma is considered the most common entity, consisting histopathologically almost exclusively of Schwann cells. Another benign tumor containing Schwann cells is ganglioneuroma. Here, ganglion cells are histopathologically apparent in addition to the Schwann cell-containing stroma. Ganglioneuroma belongs to the group of neuroblastic tumors and can occur anywhere in the pathway of sympathetic ganglion cells. In this report, we present the disease courses as well as the findings of two patients with different orbital tumors. In both cases, the diagnosis was only confirmed by histopathological examination. The first patient had a schwannoma with cystic degeneration and the second patient had a ganglioneuroma, both tumor entities which occur only rarely in the orbit. Commonalities and differences are discussed.

Increased Orbital Muscle Fraction Diagnosed by Semi-Automatic Volumetry: A Risk Factor for Severe Visual Impairment with Excellent Response to Surgical Decompression in Graves' Orbitopathy.

Graves' orbitopathy (GO) leads to increased orbital tissue and causes symptoms such as exophthalmos, functional complaints, or dysthyroid optic neuropathy. Different GO types with fat and/or muscle enlargement were identified, and increased muscle appears to particularly influence visual status and treatment response. The current study examines visual parameters dependent on orbital muscle volume fraction in a surgically treated GO cohort. After volumetric analysis of the preoperative orbital content, 83 orbits in 47 patients were categorized into predefined groups (increased or not-increased muscle fraction). All cases underwent pterional orbital decompression, and pre- and postoperative visual status was retrospectively analyzed. Forty-one orbits revealed increased and 42 orbits revealed not-increased muscle volume (mean fraction 29.63% versus (vs.) 15.60%). The preoperative visual acuity (VA) was significantly lower in orbits with increased vs. not-increased muscle volume (mean VA 0.30 vs. 0.53, difference 2.5 lines). After surgery, mean VA improved significantly by 1.7 lines in orbits with increased muscle volume. Not preoperative, but postoperative exophthalmos was significantly lower in orbits with not-increased muscle volume. Increased orbital muscle is associated with significantly reduced VA, but can be remarkably improved by pterional orbital decompression. Therefore, surgical therapy should be considered particularly in decreased VA with orbital muscle enlargement.

Spiroplasma species as a rare cause of congenital cataract and uveitis: a case series.

BACKGROUND: To date, only four cases of ocular spiroplasma infection have been reported in the entire ophthalmic literature. We add two more cases to raise awareness of this sight-threatening congenital disease that manifests as cataract with ocular inflammation. CASE PRESENTATION: Both infants were referred for cataracts associated with ocular inflammation. Case 1, a 3-week-old neonate presented with unilateral cataract, ocular inflammation and elevated intraocular pressure. Case 2 was a 3-month-old infant with bilateral cataract and panuveitis. Lensectomies with or without vitrectomy and subsequent analyses of the specimens were performed. Transmission electron microscopy and multiplex polymerase chain reaction or 16 s rRNA gene polymerase chain reaction revealed spiroplasma species. CONCLUSIONS: Spiroplasma as a very rare cause for congenital cataract might be underdiagnosed. We recommend performing polymerase chain reaction to probe for spiroplasma species in congenital cataracts with an inflammatory component.

Ophthalmological Management of Patients with Pituitary Adenomas. / Ophthalmologisches Management von Patienten mit Hypophysentumoren.

Pituitary tumours are a common cause of functional impairment and degeneration of the anterior visual pathway. Depending on localization and size, they clinically manifest as initially reversible visual field defects. As part of interdisciplinary tumour management, ophthalmologic examinations are of particular importance concerning diagnostics, indication for tumour resection and documentation of functional surgical results. Based on the relationship between clinical dysfunction and manifest atrophy, together with the patient's age and the duration of symptoms, the ophthalmologist can provide insights into the postoperative visual prognosis. Under good conditions, surgical tumour resection often results in significant improvements to visual fields and acuity. Long-term ophthalmological controls are required in cases of persistent visual loss, radiotherapy or tumour remnants abutting the visual pathway.

Surgical outcomes in patients with optic disc pit maculopathy: does peeling the ILM lead to better outcomes?

PURPOSE: Optic disc pits (ODPs) are rare congenital anomalies. Several patients develop optic disc pit maculopathy (ODP-M): visual impairment caused by intra- and/or subretinal fluid. Treatment mode remains controversial. This study was designed to investigate the effectiveness of pars plana vitrectomy (PPV) and gas tamponade with or without internal limiting membrane (ILM)-peeling in improving visual acuity and reducing subretinal fluid in ODP-M patients. METHODS: We retrospectively reviewed the charts of 16 patients who underwent surgery for ODP-M from 2002-2015. Six patients underwent PPV with gas tamponade (group 1); ten patients additionally received ILM-peeling (group 2). Pre- and postoperative visual acuity and central retinal thickness (CRT) were compared between groups, as well as retinal morphology and the number of secondary vitrectomies and complications. RESULTS: Median visual acuity improved by 2 ETDRS lines in both groups (p = 0.713, Mann-Whitney U test). Median CRT decreased by 426.5 µm and 460 µm (p = 0.931). One patient in group 1 underwent repeat vitrectomy for persistent retinoschisis. Three patients in group 2 required repeat vitrectomy: two to treat a macular hole, one for peripheral retinal holes with retinal detachment. CONCLUSION: In our cohort, PPV with gas tamponade proved to be an effective first-line treatment for ODP-M. Additional ILM-peeling did not give a significant benefit in this study.

[Corneal Changes in Infancy and Childhood as an Expression of Systemic Metabolic Diseases]. / Hornhautveränderungen im Säuglings- und Kindesalter als Ausdruck systemischer Stoffwechselerkrankungen.

Bilateral corneal opacities can be a leading symptom of different systemic diseases. Especially in childhood, various metabolic diseases, although very rare, should be considered as a possible diagnosis. Since corneal opacities can be among the first clinical symptoms of these diseases, the ophthalmologist plays a central role in initiating early interdisciplinary diagnostics. The early diagnosis is extremely important for further prognosis and the clinical outcome of the affected patients due to the early initiation of therapy.

[Use of the Multidisciplinary Specialised Case Conference at the Freiburg Orbital Centre]. / Inanspruchnahme der multidisziplinären spezialisierten Fallkonferenz im Freiburger Orbitazentrum.

BACKGROUND: The treatment of tumors increasingly takes place in specialised interdisciplinary centres. Therapeutic decisions are usually made at case conferences. Ophthalmologists, oromaximillofacial surgeons, ENT physicians, neurosurgeons, as well as pediatricians, radiotherapists and radiologists are all involved in the treatment of orbital diseases. The aim of this article is to present the concept of a multidisciplinary case conference for orbital diseases and to analyse case numbers, indications, and the influence on the patient's therapy. METHODS: We analysed an anonymized data set of patients who presented in the case conference of the University Hospital Freiburg from 2008 to 2018 with regard to clinical diagnosis, histological diagnoses, number of surgical interventions, and number of interdisciplinary therapy decisions. RESULTS: From 2008 to 2018, 545 patients were presented in a weekly conference. Of these, 453 were available for anonymous evaluation. The median age was 56 years (quartiles 41; 69). The most frequent indication was an orbital tumour of unclear malignancy (n = 52; 11%). Further indications included Grave's orbitopathy (n = 39; 9%), orbital pseudotumour (n = 36; 8%), cranial nerve palsy (n = 22; 5%), and orbital lymphoma (n = 22; 5%). The most frequent histological diagnoses were B-cell lymphoma (n = 10; 2%), venous malformation (cavernoma, n = 8; 2%), marginal zone lymphoma (n = 8; 2%), and squamous cell carcinoma (n = 6; 1%). An interdisciplinary therapeutic approach was defined for 174 patients. CONCLUSION: A high demand for the interdisciplinary case conference was demonstrated. The high rate of primary or secondary interdisciplinary decisions indicates the value of such a conference. Hence, the patient is spared multiple examinations in the individual specialist areas and quick and effective therapy decisions can be achieved.

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release.

PURPOSE: Retinal ischemia induces apoptosis leading to neurodegeneration and vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI). These effects were also demonstrated for the intravenously administered CO-releasing molecule (CORM) ALF-186. This article summarizes the results of intravitreally released CO to assess its suitability as a neuroprotective and neuroregenerative agent. METHODS: Water-soluble CORM ALF-186 (25 µg), PBS, or inactivated ALF (iALF) (all 5 µl) were intravitreally applied into the left eyes of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected and were used for comparison. Retinal tissue was harvested 24 h after intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38, HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-α, and GAP-43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The ability of RGC to regenerate their axon was evaluated two and seven days after IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was used to analyze the different cell types growing out of the retinal explants. RESULTS: Compared to the RGC-density in the contralateral right eyes (2804±214 RGC/mm2; data are mean±SD), IRI+PBS injection resulted in a remarkable loss of RGC (1554±159 RGC/mm2), p<0.001. Intravitreally injected ALF-186 immediately after IRI provided RGC protection and reduced the extent of RGC-damage (IRI+PBS 1554±159 vs. IRI+ALF 2179±286, p<0.001). ALF-186 increased the IRI-mediated phosphorylation of MAP-kinase p38. Anti-apoptotic and anti-inflammatory effects were detectable as Caspase-3, NF-kappaB, TNF-α, and AIF-1 expression were significantly reduced after IRI+ALF in comparison to IRI+PBS or IRI+iALF. Gap-43 expression was significantly increased after IRI+ALF. iALF showed effects similar to PBS. The intrinsic regenerative potential of RGC-axons was induced to nearly identical levels after IRI and ALF or iALF-treatment under growth-permissive conditions, although RGC viability differed significantly in both groups. Intravitreal CO further increased the IRI-induced migration of GFAP-positive cells out of retinal explants and their transdifferentiation, which was detected by re-expression of beta-III tubulin and nestin. CONCLUSION: Intravitreal CORM ALF-186 protected RGC after IRI and stimulated their axons to regenerate in vitro. ALF conveyed anti-apoptotic, anti-inflammatory, and growth-associated signaling after IRI. CO's role in neuroregeneration and its effect on retinal glial cells needs further investigation.

Visual field defects following different resective procedures for mesiotemporal lobe epilepsy.

INTRODUCTION: One of the most common side effects of mesiotemporal lobe resection in patients with medically intractable epilepsy are visual field defects (VFD). While peripheral defects usually remain unnoticed by patients, extended VFD influence daily life activities and can, in particular, affect driving regulations. This study had been designed to evaluate frequency and extent of VFD following different surgical approaches to the mesiotemporal area with respect to the ability to drive. MATERIALS AND METHODS: This study comprises a consecutive series of 366 patients operated at the Epilepsy Center in Freiburg for intractable mesiotemporal lobe epilepsy from 1998 to 2016. The following procedures were performed: standard anterior temporal lobectomy (ATL: n=134; 37%), anterior temporal or keyhole resection (KH: n=53; 15%), and selective amygdalohippocampectomy via the transsylvian (tsAHE: n=145; 40%) and the subtemporal (ssAHE: n=34; 9%) approach. Frequency and extent of postoperative VFD were evaluated in relation to different surgical procedures. According to the German driving guidelines, postoperative VFD were classified as driving-relevant VFD with the involvement of absolute, homonymous central scotoma within 20° and driving-irrelevant VFD with either none or exclusively minor VFD sparing the center. RESULTS: Postoperative visual field examinations were available in 276 of 366 cases. Postoperative VFD were observed in 202 of 276 patients (73%) and were found to be driving-relevant in 133 of 276 patients (48%), whereas 69 patients (25%) showed VFD irrelevant for driving. Visual field defects were significantly less likely following ssAHE compared with other temporal resections, and if present, they were less frequently driving-relevant (p<0.05), irrespective of the side of surgery. CONCLUSION: Subtemporal sAHE (ssAHE) caused significantly less frequently and less severely driving-relevant VFD compared with all other approaches to the temporal lobe, irrespective of the side of surgery.

Die randunscharfe Papille: eine diagnostische Herausforderung.

Correct differential diagnosis in cases of blurred optic disc margins is a challenging task for ophthalmologists. The reliable differentiation of pseudopapilloedema and true papilloedema has significant implications for proper patient management. Conditions that give rise to pseudopapilloedema include small crowded discs, tilted discs and optic nerve head drusen. Conditions that cause bilateral true swelling of the optic nerve head with initially good visual acuity include those that are secondary to raised intracranial pressure (optic disc edema, ODE). The majority of cases, however, present with unilateral optic nerve head swelling and normal intracranial pressure. They have systemic signs or symptoms which either precede ocular manifestation or have ophthalmoscopic signs other than elevation of the optic disc pointing to its diagnosis. Ancillary testing has been utilized to aid in identification of true ODE or swelling, including ultrasonography, fluorescein angiography, cranial and orbital MRI with venography, and lumbar puncture. Optical coherence tomography is also evolving as a modality for differentiation of buried optic disc drusen from ODE. This presentation will discuss each modality, with examples, advantages, and disadvantages for each.

Carbon monoxide treatment reduces microglial activation in the ischemic rat retina.

PURPOSE: Ischemia and reperfusion (I/R) injury damages retinal neurons. Retinal injury is accompanied by activation of microglia, which scavenge the dead or dying neurons, but increasing evidence now indicates that amoeboid-shaped microglia cells activated in the brain after ischemia have neurotoxic and damaging properties in their own right. A previous study showed that postconditioning with carbon monoxide (CO) protects retinal ganglion cells (RGCs) after I/R through anti-apoptotic and anti-inflammatory mechanisms. The present study was designed to investigate and quantify the activation of retinal microglia after I/R with and without CO postconditioning. METHODS: Adult Sprague-Dawley rats underwent retinal ischemia by increasing the ocular pressure to 120 mmHg for 1 h through a needle inserted into the anterior chamber. Reperfusion was induced by removing the needle. After I/R, one group of animals was kept in a CO (250 ppm) atmosphere for 1 h; the other group was kept in room air (Air). At 1, 2, 3, and 7 days after I/R, the eyes were enucleated and fixed. Intracardiac blood was analyzed for systemic effects of CO or I/R. Retinal cross sections were taken from the middle third of the eye and were stained with anti-Iba-1. Microglia cells were graded as amoeboid or ramified phenotypes according to morphologic criteria. Retinal thicknesses were determined. RESULTS: Evaluation of retinal tissue revealed a significant reduction of amoeboid microglia cells after I/R + CO when compared to the I/R + Air group. The peak number of amoeboid microglia was observed at day 2 post-I/R + Air. This rise was attenuated by CO postconditioning (815 versus 572 cells/mm2 for I/R + Air versus I/R + CO, respectively; p = 0.005). CO reduced and further postponed the peak in the numbers of amoeboid and ramified microglia cells in ischemic eyes and prevented microglial activation in the contralateral eyes. I/R-induced leucocytosis was inhibited by CO inhalation. The reduction of retinal thickness after I/R was more serious after Air inhalation when compared to the CO group. CONCLUSIONS: Numerous activated microglia cells appear in the inner retina after I/R, and CO-treatment significantly attenuates this glial response. Antagonism of microglial activation may be a further neuroprotective effect of CO, apart from its direct anti-apoptotic capacity.

Neuroprotective effects of Argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells.

Retinal ischemia and reperfusion injuries (R-IRI) damage neuronal tissue permanently. Recently, we demonstrated that Argon exerts anti-apoptotic and protective properties. The molecular mechanism remains unclear. We hypothesized that Argon inhalation exert neuroprotective effects in rats retinal ganglion cells (RGC) via an ERK-1/2 dependent regulation of heat-shock proteins. Inhalation of Argon (75 Vol%) was performed after R-IRI on the rats' left eyes for 1 h immediately or with delay. Retinal tissue was harvested after 24 h to analyze mRNA and protein expression of heat-shock proteins -70, -90 and heme-oxygenase-1, mitogen-activated protein kinases (p38, JNK, ERK-1/2) and histological changes. To analyze ERK dependent effects, the ERK inhibitor PD98059 was applicated prior to Argon inhalation. RGC count was analyzed 7 days after injury. Statistics were performed using anova. Argon significantly reduced the R-IRI-affected heat-shock protein expression (p < 0.05). While Argon significantly induced ERK-1/2 expression (p < 0.001), inhibition of ERK-1/2 before Argon inhalation resulted in significantly lower vital RGCs (p < 0.01) and increase in heme-oxygenase-1 (p < 0.05). R-IRI-induced RGC loss was reduced by Argon inhalation (p < 0.001). Immunohistochemistry suggested ERK-1/2 activation in Müller cells. We conclude, that Argon treatment protects R-IRI-induced apoptotic loss of RGC via an ERK-1/2 dependent regulation of heme-oxygenase-1. We proposed the following possible mechanism for Argon-mediated neuroprotection: Argon exerts its protective effects via an induction of an ERK with subsequent suppression of the heat shock response. In conclusion, ischemia and reperfusion injuries and subsequent neuronal apoptosis are attenuated. These novel findings may open up new opportunities for Argon as a therapeutic option, especially since Argon is not toxic.

Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

PURPOSE: Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye. METHODS: IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA. RESULTS: IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001). Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01), as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001). Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%. CONCLUSION: Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

Orbital reconstruction: prefabricated implants, data transfer, and revision surgery.

External impact to the orbit may cause a blowout or zygomatico-maxillary fractures. Diagnosis and treatment of orbital wall fractures are based on both physical examination and computed tomography scan of the orbit. Injuries of the orbit often require a reconstruction of its orbital walls. Using computer-assisted techniques, anatomically preformed orbital implants, and intraoperative imaging offers precise and predictable results of orbital reconstructions. Secondary reconstruction of the orbital cavity is challenging due to fractures healed in malposition, defects, scarring, and lack of anatomic landmarks, and should be avoided by precise primary reconstruction. The development of preformed orbital implants based on topographical analysis of the orbital cavity was a milestone for the improvement of primary orbital reconstruction.

Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina.

PURPOSE: Ischemia and reperfusion injury (I/R) of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO) after I/R injury ('postconditioning') would protect retinal ganglion cells (RGC). METHODS: Retinal I/R injury was performed in Sprague-Dawley rats (n = 8) by increasing ocular pressure (120 mmHg, 1 h). Rats inhaled room air or CO (250 ppm) for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF)-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg). Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining. RESULTS: Inhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9 ± 0.3 vs. 1.4 ± 0.2, p = 0.028; caspase-3: 2.0 ± 0.2 vs. 1.5 ± 0.1, p = 0.007; mean ± S.D., fold induction at 12 h), while expression of Bcl-2 was induced (1.2 ± 0.2 vs. 1.6 ± 0.2, p = 0.001; mean ± S.D., fold induction at 12 h). CO postconditioning suppressed retinal p38 phosphorylation (p = 0.023 at 24 h) and induced the phosphorylation of ERK-1/2 (p<0.001 at 24 h). CO postconditioning inhibited the expression of HO-1. The activation of NF-κB, microglia and Müller cells was potently inhibited by CO as well as immigration of proliferative microglia and macrophages into the retina. CO protected I/R-injured RGC with a therapeutic window at least up to 3 h (n = 8; RGC/mm(2); mean ± S.D.: 1255 ± 327 I/R only vs. 1956 ± 157 immediate CO treatment, vs. 1830 ± 109 1.5 h time lag and vs. 1626 ± 122 3 h time lag; p<0.001). Inhibition of ERK-1/2 did not counteract the CO effects (RGC/mm(2): 1956 ± 157 vs. 1931 ± 124, mean ± S.D., p = 0.799). CONCLUSION: Inhaled CO, administered after retinal ischemic injury, protects RGC through its strong anti-apoptotic and anti-inflammatory effects.

Evaluation of intraocular pressure elevation in a modified laser-induced glaucoma rat model.

The main drawbacks of currently described pressure induced glaucoma animal models are, that intraocular pressure (IOP) either rises slowly, leading to a heterogeneous onset of glaucoma in the treated animals or that IOP normalizes before significant damage occurs, necessitating re-treatment. Furthermore, a variable magnitude of IOP increase often results when particles are introduced into the anterior chamber. In order to develop a simple and reproducible rat glaucoma model with sustained IOP elevation after a single treatment we induced occlusion of the chamber angle by anterior chamber paracentesis and subsequent laser coagulation of the limbal area with 35, 40 or 45 laser burns. Right eyes served as controls. IOP was measured three times weekly using TonoLab rebound tonometry in awake animals. After four weeks, retinal tissue was harvested and processed for whole mount preparation. The number of prelabeled, fluorogold-positive retinal ganglion cells (RGCs) was analyzed under a fluorescence microscope. The eyes were further analyzed histologically. Results are expressed as means and standard deviation. Amplitude and duration of the IOP elevation increased with the number of laser burns. Two weeks after 35, 40 or 45 translimbal laser burns the IOP difference between treated and control eye was 7.5 ± 5, 14 ± 8 or 19 ± 9 mmHg, respectively; the RGC density/mm(2) 28 days after treatment was 1488 ± 238 for control eyes (n = 31) and 1514 ± 287 (n = 10), 955 ± 378 (n = 10) or 447 ± 350 (n = 11) for the respective laser groups. Mean IOP of all control eyes over the observation period was 12.4 ± 0.8 mmHg. The chamber angle showed pigment accumulation in the trabecular meshwork of all laser groups and confluent peripheral anterior synechia after 40 and 45 laser burns. Histologic examination of the retina revealed increasing glia activation in a pressure dependant manner. In this study, >91% of laser treated rats developed secondary glaucoma with sustained IOP elevation for at least 2 weeks. The amount of IOP elevation and RGC loss correspond with the number of laser burns applied. This relatively high success rate after a single procedure may constitutes an advantage over established glaucoma models, as this decreases the risk of complications (e.g. corneal decompensation, intraocular bleeding or inflammation) and, thus, improves the outcome.