bluuebunny/crossref_metadata_2025 huggingface dataset:
The response of squamous cell carcinoma of the conjunctiva to treatment with photodynamic therapy
Authors: BARBAZETTO IA , LEE TC , ABRAMSON DH
Published: October 2007

Purpose: Photodynamic therapy (PDT) was originally developed for tumor treatment. Based on initial promising animal studies, we investigated the clinical use of PDT for treating conjunctival neoplasia.

Methods: Patients with newly diagnosed or recurrent conjunctival neoplasia / squamous cell carcinoma of the conjunctiva (SCC) were treated as part of an interventional case series. Patients received one to three treatments of 6 mg/m2 body surface area verteporfin (Visudyne, Novartis Ophthalmics, Switzerland) intravenously. The light dose was calculated as 50 J/cm2. All tumors were irradiated 1 minute after a bolus injection. Patients were followed weekly and then in monthly intervals up to 1 year. Retreatment was performed as early as one months after the initially treatment based on clinically and angiographic exam.

Results: Angiographic occlusion of the tumor vasculature was usually observed one week after treatment. Signs of tumor regression were seen in all patients one month after treatment. Highly vascularized (papillomatous) lesions showed the most dramatic response to treatment. PDT was well tolerated with only minimal side‐effects including mild ocular irritaion, subconjunctival hemorrhage, chemosis and one case of infusion related back‐pain. No conjunctival scaring, thinning or scleral thinning were observed following treatments.

Conclusions: Photodynamic therapy could potentially offer a less invasive approach to treating non‐melanotic conjunctival lesions in a subset of patients. However, larger studies are warranted to assess optimal treatment parameters and long‐term tumor control.
Reconstruction of the congenital anophthalmic/crytophthalmic socket
Authors: BRISCOE D , VARDIZER M
Published: October 2007

Purpose: We discuss considerations and the difficulties encountered in socket reconstruction of three cases of congenital anophthalmic /cryptophthalmic socket.

Methods: 3 cases of congenital anophthalmic / cryptophthalmic socket underwent surgery following a period of socket expansion using prosthesic expanders. 2 cases had socket reconstruction using baseball implant and buccal mucous membrane grafting , and the third case had socket expansion surgery by lateral orbital wall burring and buccal mucous membrane grafting.

Results: The 2 cases with baseball implants had late postoperative problems. One case had implant migration causing lower eyelid ectropion, and chronic infections. The second case had an over prominent implant causing difficulty with eyelid closure which became worse over one year. Both cases underwent further surgery with implant exchange for Dermis Fat Grafts, giving satisfgactory results. The third case had an initially good result, but with growth of his head the orbit remained smaller than the other side.

Conclusions: We recommend the primary use of Dermis Fat Graft in congenital anophthalmic / cryptophthalmic sockets and in our opinion baseball implants should not be used in these cases. In our experience Buccal Mucous membrane grafting has only limited success in these cases.
Treating ocular surface squamous neoplasia by topical Mitomycin C
Authors: FRUCHT‐PERY J , PE'ER J
Published: October 2007

Purpose: Ocular surface squamous neoplasia, which include conjunctival epithelial dysplasia, carcinoma‐in‐situ and invasive squamous cell carcinoma and which may involve also the cornea, were traditionally treated by surgical excision with the possible addition of cryotherapy, local irradiation, or external beam irradiation. Since 1992 we have treated the intraepithelial types of OSNN by topical Mitomycin C. Other centers have followed our steps. We will describe our and others' experience using this type of treatment.

Methods: Our protocol for treating intraepithelial OSSN consists of applying 0.02% (0.2 μg/ml) Mitomycin drops four times daily for two weeks, with additional such courses if needed, including a two‐week intermission between the courses.

Results: About 95% of our patients with intraepithelial OSSN responded to this treatment. About half of them needed only one course of two weeks, about 35% needed two courses, and the rest needed 3 to 5 courses. In those patients with corneal involvement, marked improvement of the visual acuity was noticed. Main side effects were conjunctival hyperemia and corneal epitheliopathy. No permanent complications were noticed.

Conclusions: Topical Mitomycin C is an effective and safe method for treating intraepithelial OSSN with relatively mild and temporary side effects. It can replace the surgical approach, especially for lesions that spread over large areas of conjunctiva and cornea and necessitate extensive excision.
Treating conjunctival primary acquired melanosis with atypia by topical Mitomycin C
Authors: PE'ER J , FRUCHT‐PERY J
Published: October 2007

Purpose: Conjunctival primary acquired melanosis can appear with or without atypia. The lesions with atypia can become transformed to melanoma, and some consider them as melanoma‐in‐situ. The PAM lesion shows waxing and waning, and its boundaries are difficult to detect. Therefore, one can never be sure that the lesion was totally excised by the traditional method of surgical excision and cryotherapy. Since 1994 we have been treating our patients with PAM with atypia proven by biopsy, with topical Mitomycin C. Other centers have used the same methods. We will describe our experience in using this method of treatment.

Methods: The protocol we have been using consists of 0.04% (0.4 μg/ml) Mitomycin C drops four times daily for two weeks. Currently we apply 3 such courses, with two weeks' intermission between courses.

Results: The vast majority of our patients showed partial or complete disappearance of the pigmentation. One patient had recurrence of the PAM and in one patient the recurrence was in the form of conjunctival melanoma. The main side effects were temporary conjunctival hyperemia and corneal epitheliopathy. In two patients the epitheliopathy was severe and longstanding, possibly due to limbal stem‐cell deficiency following a higher concentration of the Mitomycin C drops.

Conclusions: Topical Mitomycin C chemotherapy can be used as a good alternative to surgical excision and cryotherapy in treating conjunctival PAM with atypia, with reasonable side effects. We recommend not to use this method in treating invasive conjunctival melanoma.
Using intravitreal methotrexate for treating vitreoretinal lymphoma
Authors: PE'ER J , SIEGAL T , FRENKEL S
Published: October 2007

Purpose: Vitreoretinal involvement occurs in approximately one‐quarter of patients with primary CNS lymphoma (PCNSL), and in some patients with systemic lymphoma who may later develop CNS lymphoma. The traditional method for treating vitreoretinal lymphoma, which is the common type of intraocular lymphoma, is by external beam radiation, or intravenous or intrathecal chemotherapy; however, recurrences are common. We describe our ten years of experience in treating vitreoretinal involvement of PCNSL by intravitreal injections of methotrexate (MTX).

Methods: Biopsy‐proven vitreoretinal lymphoma has been treated by intravitreal injections of 400 μg/ml methotrexate. According to our protocol, injections are administered twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months for a total of 25 injections.

Results: Forty‐four eyes of 26 patients have been treated; 7 patients had monocular involvement and 19 binocular. Twenty‐three patients had B‐cell lymphoma and 3 patients had T‐cell lymphoma. In all patients remission of the intraocular lymphoma was achieved after 6.1 + 3.5 injections (range 2 – 16 injections). None of the patients had an intraocular recurrence. Among the side effects, the most common were conjunctival hyperemia and corneal epitheliopathy, which usually subsided when the interval between the injections increased.

Conclusions: In our experience, treatment by intravitreal injections of methotrexate provides complete remission of vitreoretinal lymphoma with, so far, no recurrences and with bearable side effects, and can be considered as alternative treatment to radiotherapy and systemic or intrathecal chemotherapy.
Neuro‐ophthalmological analysis and imaging of optic nerve tumours
Authors: MILEA D
Published: October 2007

Purpose: To describe correlations between the clinical manifestations and the neuro‐radiological features of optic nerve tumors.

Methods: Description of the available radiological techniques for the appropriate evaluation of an optic nerve tumor. MR imaging of the orbit is the most common method and it should include standard enhanced fat‐suppression, T1 and T2‐weighted axial and coronal images, other sequences being optional.

Results: The two most primary common optic nerve tumors are optic nerve glioma and optic nerve meningioma, other tumors (gangliogliomas, medulloepitheliomas, haemangioblastomas haemangiopericytomas, etc.) being more rare, diagnosed on pathological, not radiological grounds.

Optic nerve meningiomas, occurring most commonly in middle‐aged females, have a tubular appearance on CT or MR as opposed to the fusiform or globular shape of optic gliomas. Optic nerve sheath meningiomas are usually isointense or hypointense on T1‐weighted imaging, enhancing after contrast injection.

Metastatic carcinomas to the optic nerve are very unusual, and may be sometimes radiographically indistinguishable from optic nerve meningioma. In most of the cases a thourough history and accurate clinical examination may help the interpretation of the radiological findings, pathology being however at times necessary in atypical cases.

Conclusions: Neuro‐imaging allows most often to distinguish different types of optic nerve tumors. This is the reason why it is widely accepted now to use radiotherapy for treatment of optic nerve sheath meningiomas without pathological confirmation of the diagnosis. In individual cases with atypical clinical or radiological features, pathology is nevertheless needed for firm diagnosis.
The use of VEP in the evaluation of optic nerve lesions
Authors: HOLDER GE
Published: October 2007

Purpose: To describe the use of VEP and other electrophysiological investigations in the assessment of optic nerve function.

Methods: The techniques for recording ISCEV Standard VEP, ERG and PERG will be demonstrated. The clinical application of these techniques will be illustrated using selected cases.

Results: The nature of the VEP changes in various disorders of optic nerve function will be described. Particular emphasis will be placed on the ability of electrophysiology directly to assess the function of the retinal ganglion cells, and to facilitate, in most cases, the distinction between optic nerve and macular dysfunction.

Conclusions: The objective data provided by VEP and other electrophysiological investigations play an important role in the mangement of patients with suspected optic nerve disease.
Histopathology of optic nerve tumours
Authors: HEEGAARD S
Published: October 2007

Purpose: To evaluate the distribution in Denmark of histologically verified optic nerve lesions during a period of 60 years. Histological diagnosis, gender and age of patients were collected. Changes in frequency of parameters during the observation period were calculated.

Methods: All optic nerve lesions reported at the Eye Pathology Institute, University of Copenhagen, during the period 1940–99 were investigated. All similar lesions reported at all pathological departments in Denmark during 1974–99 were also investigated.

Results: The number of optic nerve lesions identified totalled 313 in 298 patients. The frequency of histopathological optic nerve lesions increased significantly over the last 25 years. At present, an average of 12 lesions per year is recorded. Lesions in children accounted for 42% (130). Benign tumours constituted 33% (44) of the total number of tumours in adults and 61% (62) in children. Frequencies of glioma and optic nerve sheath meningioma increased significantly during the last 25 years. Subjects presenting with optic nerve sheath meningioma exhibited a significant difference in age at presentation: the mean age of women at presentation was seen to be 48.8 years, while the mean age of men at presentation was seen to be 29.7 years. The most frequent lesion seen in children was glioma and in adults invasion from malignant uveal melanoma.

Conclusions: Histologically diagnosed optic nerve lesions are rare and consist primarily of tumours. The increase in frequency of optic nerve lesions in Denmark during the last 25 years is due to an increase in the number of benign tumours.
MMPs in ocular physiology
Authors: EICHHORN M
Published: October 2007

Purpose: Metalloproteinases (MMP) are a family of more than 20 enzymes. with the common ability to degrade extracellular matrix (ECM) components. Since MMPs may also destruct signaling molecules or release them from ECM, MMPs shape not only the structural, but also the functional aspects of a distinct ECM compartment. As a consequence MMPs are implicated in a wide range of physiological and pathological processes in the eye (e.g. corneal wound healing, AMD, diabetic retinopathy, choroidal neovascularization, and glaucomatous changes in trabecular meshwork and optic nerve head.).

This review will summerise our knowledge of MMPs in ocular tissues and our present understanding of the regulation of MMP activity.

Methods: Review of the literature.

Results: MMPs are zinc endopeptidases which can be subdivided in 4 subgroups. Collagenases process fibrillar collagen types I, II and III. Gelatinases degrade basement membrane collagen types IV and V. Stromlysins recognize nonfibrillar collagens, laminin, fibronectin and proteogylcans. Recently, membrane type MT‐MMPs were detected bound to cell membranes.

MMP activity is controlled basically on three levels. Synthesis is regulated by transcription factors. Secreted, inactive proMMPs must be activated, mainly by plasmin. Plasmin itself is regulated by plasminogen activators (PA) and their counterpart plasminogen activator inhibitors (PAI). Finally, active MMPs may be blocked by tissue inhibitors of MMPs (TIMPs).

Conclusions: The variety of MMPs, their ubiquitous presence and their broad range of substrates develop a complex system with tight regulation on several levels. To date our understanding is far from satisfying and further work is necessary to reach a more comprehensive look especially at the biological impact of this family of enzymes.
MMPs in CNV
Authors: LAMBERT V , RAKIC JM , NOEL A , FOIDART JM
Published: October 2007

Purpose: Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 are increased in human choroidal neovascularization (CNV) occurring during the exudative most aggressive form of age‐related macular degeneration (AMD), but their precise role and potential interactions remain unclear.

Methods: To address the question of MMP‐2 and MMP‐9 functions, mice deficient in the expression of MMP‐ 2 (MMP‐2 KO), MMP‐9 (MMP‐9 KO), and both MMP‐2 and MMP‐9 (MMP‐2,9 KO) with their corresponding wild‐type mice (WT) underwent CNV induction by laser‐induced rupture of the Bruch’s membrane.

Results: Both the incidence and the severity of CNV were strongly attenuated in double deficient compared with single gene deficient mice or corresponding WT controls. The reduced neovascularization was accompanied by fibrinogen/fibrin accumulation. Furthermore, overexpression of the endogenous MMP inhibitors TIMP‐1 or TIMP‐2 (delivered by adenoviral vectors) in WT mice or daily injection of a synthetic and gelatinase selective MMP inhibitor (Ro 26‐2853) significantly decreased the pathological reaction.

Conclusions: These findings suggest that MMP‐2 and MMP‐9 may cooperate in the development of AMD and that their selective inhibition represents an alternative strategy for the treatment of choroidal neovascularization.
Fluorescein and ICG angiograms : still a gold standard
Authors: O’TOOLE L
Published: October 2007

Purpose: To review the role of Fluorescein Angiography and ICG in the management of ARMD

Methods: Fundus Fluorescein Angiography (FFA) is the gold standard for classification of Choroidal Neovascular Membranes (CNVMs) in Age Related Macular Degeneration (ARMD). CNVMs may be defined as classic, minimally classic or occult by their filling patterns observed on angiography. The findings of the large TAP and VIP studies are based on angiographically defined CNVMs. FFA in the setting of ARMD is indicated when the patient complains of new metamorphopsia, experiences unexplained blurred vision or there is evidence of subretinal fluid, haemorrhages or hard exudates1,2 .

Fluorescein Angiography is an invasive procedure and carries a risk of anaphylaxis and death. There should be on site facilities readily available to manage any potential complications of an FFA.

Indocyanine Green Angiography (ICG) is used to evaluate the choroidal circulation and is of particular use in the diagnosis of Idiopathic Polypoidal Choroidal Vasculopathy.

Results: With the advent of new therapeutic modalities there is a need for frequent monitoring of the response of the CNVM to treatment. Ocular Coherence Topography complements FFAs and ICG, reducing the number of angiograms required during the quiescent phase of treatment. In spite of this invasive angiography remains the gold standard for diagnosis and treatment

Conclusions: References

1 Summary benchmarks for Preferred Practice Benchmarks in the Setting of ARMD. www.aao.org

2 International Clinical Guidelines for ARMD. www.icoph.org
Phenotype‐Genotype correlations : more than identifying risks ?
Authors: AUDO I , LEVEILLARD T , SAHEL JA
Published: October 2007

Purpose: To critically review current knowledge on genetic susceptibility for AMD and its relevance in a clinical setting.

Methods: AMD is a multifactorial disorder with both environmental and genetic risk factors. Genetic knowledge of the disease made a real breakthrough in 2005 after 3 concomitant publications incriminating complement factor H (CFH) as a susceptibility gene, confirming the major role of inflammation in the disease pathogenesis. Further studies suggested the existence of other susceptibility genes, such as the C2/Complement Factor B or LOC387715/PLEKHA1/HTAR1. Identification of other susceptibility genes is expected and groups, including ours, are putting together large cohorts of patients using an unbiased genome wide scan (GWS) approach. Discovery of new genes will generate potential molecular targets useful to develop novel therapeutic approaches. However, these new genetic findings raised different questions that will be discussed based on our experience and the current literature:

‐ How can we refine correlation analysis between specific susceptibility alleles, environmental factors, systemic biomarkers and specific subgroups of AMD? In particular, how pertinent are the current AMD classifications to outline these correlations and should new classifications, based for instance on OCT, fundus autofluorescence patterns or functional data, be generated?

‐ Due to the important relative risk associated with the CFH or LOC387715 susceptibility allele and regarding the coast of genotyping approaches such as GWS, how can we narrow down the targeted population to increase the likelihood of finding new susceptibility genes?

‐ Is a systematic genotyping strategy for CFH and LOC387715 of any AMD patient relevant in a clinical setting?
Microperimetry : understanding what went wrong or predicting therapeutic routes
Authors: VUJOSEVIC S
Published: October 2007

Purpose: To investigate macular sensitivity and fixation patterns with automatic fundus perimetry (microperimetry) in patients with early and late age‐related macular degeneration (ARMD).

Methods: A hundred and twenty eyes of 101 consecutive patients with early ARMD or with subfoveal choroidal neovascularization (CNV) secondary to ARMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (MP1, Nidek Technologies, Padova, Italy) was used to quantify macular sensitivity and fixation patterns (location and stability).

Results: Macular sensitivity was significantly decreased over large drusen and over pigment abnormalities (p<0.0001) and in patients with CNV when compared to normal age‐related values (p<0.0001). Fixation moved from central to eccentric and from stable to unstable in patients with active CNV, (p<0.001 and p<0.05) respectively. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (p>0.05). In cases that responded to treatment retinal sensitivity and fixation characteristics improved significantly, (p<0.05).

Conclusions: Microperimetric quantification of macular sensitivity and fixation patterns in eyes with early and late ARMD offers new data about the impact of visual impairment in these eyes. In retinal areas affected by early ARMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow early detection of functional impairment due to these lesions. Moreover, microperimetry may be of value in predicting the outcome of CNV when different treatments (laser, PDT, anti‐VEGF drugs, macular translocation and RPE transplants) are planned in current or future studies
A system to perform quantitative fluorescein angiography
Authors: SCHWARTZ A
Published: October 2007

Purpose: To develop a system with which fluorescein angiograms may be quantitatively compared across time, patients and laboratories.

Methods: Sets of standard solutions of the fluorescein were developed in media that mimics the physical and chemical environments of compartments of the eye, i.e., serum and vitreous, in which the measurement is taken. Images from these sets of standards were obtained at exactly the same time and under the same instrument settings as the data from the eye on the same angiogram. Computer software was developed to quantitatively analyze the angiogram that established calibration plots and converted the grey image to an absolute color scale image of the data, as well as provide quality control information as to the performance of the instrument.

Results: The position and shape of the excitation and emission spectra of the fluorescein standards matched those of fluorescein in serum and vitreous media. The 80% reduction in quantum efficiency of fluorescein in serum compared to fluorescein in PBS at pH 7.4 was equal to fluorescein in synthetic serum and/or PBS at pH 5.5. The reduction in quantum efficiency of fluorescein in vitreous was only 3% and equal to fluorescein in PBS at pH 7.3.

The resulting computer generated color scale angiogram images were directly compared across time and patients and the initial results appeared consistent and reasonable. In addition, by evaluating the calculated instrument performance parameters, e.g., linearity, dynamic range, detection threshold and Window of Anaylsis, a determination of the quality of the angiogram could be made.

Conclusions: This system provides data that is independent of the instrument and operator, and promises that quantitative comparisons can be made across time, patients and laboratories.
Instrumentation adaptation for quantitative fluorescein angiograms
Authors: BERNARDES R
Published: October 2007

Purpose: To obtain quantitative fluorescein angiograms that are independent of instrument setup and operator influence.

Methods: Sets of five standard fluorescein solutions were developed to mimic the environmental conditions of the plasma and vitreous compartments. Images from the eye fundus (after patient dye administration) and from these fluorescein solutions were simultaneously obtained at different focal planes via a beam splitter and lens system attached to an HRA scanning laser ophthalmoscope. Software was developed to calculate calibration plots and to convert the angiography gray‐scale images into absolute concentration image maps for both eye compartments. This methodology provided instrument calibration data for each image obtained.

Results: A system of standards, beam splitting adaptor and software was developed which provides quantitative data on an absolute color scale derived from calibration standards which are designed to provide information that is independent of the instrument and operator. Such quantitative data would be comparable across patients, laboratories and time.

Conclusions: This methodology provides a breakthrough in fluorescence angiography in that it allows direct comparison between different fluorescein angiograms either from the same patient over time or across patients and laboratories.
Recent advances in the analysis of non vascular features in retinal images
Authors: RUGGERI A , FIORIN D
Published: October 2007

Purpose: To problem of detecting non vascular dark lesions (haemorrhages and microaneurysms) in retinal images for diagnostic purposes is addressed.

Methods: The green channel of images is extracted and then normalized by compensating the luminosity and contrast drifts. The detection of clusters of dark pixels is based first on a local thresholding to identify pixels darker than the surrounding, followed by an evaluation of their spatial density, which tells how much the neighborhood of the pixel is dense of similar (dark) pixels. A further threshold is then applied to this density to identify candidate clusters of dark pixels.

Results: In a pool of 60 50‐deg fundus images acquired on slide, and then digitized with a 1378 dpi resolution, true colour, 6 images presented microaneurysms or haemorrhages. These images were chosen to evaluate the performance of the proposed method. On average, the algorithm was able to detect at least part of a lesion for 94% of the lesions present in an image. When an image presented only one lesion, so that a hit‐or‐miss situation may compromise the clinical evaluation, the algorithm was able to correctly identify the true candidate.

Conclusions: A novel, high sensitivity algorithm for identifying dark lesions in retinal images is presented. It exploits both the local gray‐level information for a first segmentation and the spatial density of segmented pixels to obtain a measure of a region homogeneity. The effectiveness of the algorithm has been successfully tested on six retinal images presenting dark lesions of various shapes and dimensions. This suggest that it can be well suited as first stage of a dark lesion detection system, which will be followed by a classification stage, able to reject possible false candidates.
Advances in the detection of the retinal vasculature
Authors: HUNTER A , AL DIRI B
Published: October 2007

Purpose: The detection and measurement of retinal vessels is discussed.

Methods: A model based on fitting “ribbon of twin” active contour models, that sandwich the vessel edges between contours pulled together by forces, is used. The use of these twins, with a constraining force maintaining approximate vessel width, serves to avoid errors instituted by a variety of noise sources.

Results: The method detects vessel segments with high reliability, and is able to measure the vessel width to within sub‐pixel accuracy. We present results comparing the performance with reference standard measurements constructed by a number of human assessors.

Conclusions: Retinal vascular measurements are potentially extremely useful in the diagnosis of a number of disease.
Retinal pigment epithelial cells under oxidative stress
Authors: WELGE‐LUSSEN U
Published: October 2007

Purpose: Various studies have demonstrated that cellular senescence may be accelerated by stress factors such as oxidative stress and transforming growth factor‐beta (TGF‐ß). This phenomenon has been termed ‘stress‐induced premature senescence (SIPS). The goal of the present study was to determine whether oxidative stress and TGF‐ß might induce SIPS in cultured human retinal pigment epithelium (RPE) cells.

Methods: Cultured human RPE cells were exposed to hydrogen peroxide (H2O2). Additionally, cells were treated with 1 ng/ml TGF‐ß1 and ‐ß2 for 48 hours. Senescence‐associated beta‐galactosidase (SA‐ß‐Gal) activity was detected by histochemical staining. Expression of SA genes apolipoprotein J (Apo J), Connective Tissue Growth Faktor (CTGF), fibronectin, SM22 were examined by real‐time PCR. Senescence‐associated signal transduction proteins (p16, p21, pRb) were analyzed by western‐blotting. Levels of TGF‐ß1 and ‐ß2 were analyzed by real‐time PCR analysis and ELISA. The effect of TGF‐ß blocking on the oxidative stress‐induced expression of senescence‐associated biomarkers was investigated by with neutralizing antibodies against pan‐TGF‐ß and TGF‐ßII receptors.

Results: H2O2 increased SA‐ß‐Gal activity by up to 10 fold and the expression of SA genes by 3‐4 folds. Treatment with TGF‐ß1 and ‐ß2 showed similar fold changes. H2O2 and TGF‐ß 1 and TGF‐ß2 markedly enhanced the expression of p16 and p21. Parallel there was an downregulation of pRb expression. Neutralizing antibodies against prevented the oxidative stress‐mediated elevation of SA biomarkers.

Conclusions: Oxidative stress and TGF‐ß are capable to induce SIPS in cultured human RPE cells. Therefore, reduction of oxidative stress and minimizing TGF‐ß may help to prevent SA changes in the RPE of early AMD
Proteolysis in RPE cells
Authors: KAARNIRANTA K
Published: October 2007

Purpose: Most cellular proteins are continuously synthesized and degraded within the life‐span of a cell. Two major systems take care of protein degradation in eukaryotic cells: the proteasomes, which degrade the vast majority of long‐ and short‐lived normal and abnormal intracellular proteins and the lysosomes, which degrade membrane and endocytosed proteins. Macroautophagy, microautophagy or chaperone‐mediated autophagy are the principal forms of lysosomal degradation in mammalian cells. In macroautophagy, cytoplasmic structures are degradated within an autophagosomes. Connection of stress inducible Hsp70, lysosomes and proteasomes were evaluated in the protein aggregation in human RPE cells.

Methods: Western blotting, immunofluorescence, transmission electron microscopy, confocal microscopy, hsp70 mRNA interference, GFP‐Hsp70 overexpression techniques were used to study proteolysis in ARPE‐19 cells.

Results: MG–132 proteasome inhibitor caused robust accumulation of Hsp70 protein and Ub protein conjugates in ARPE–19 cells. At both the Hsp70 and Ub colocalized with the protein aggregates. The granulation of juxtanuclear aggregation was clearly increased in response to proteasome inhibition and simultaneous hsp70 mRNA interference. Interestingly, we found that juxtanuclear protein aggregation is an interim, because a cease of proteasome inhibition leads to autophagosome‐mediated cleaning of cytoplasmic protein aggregates. The Hsp70 colocalization was observed in both primary lysosomal fractions and in autophagosomes.

Conclusions: The Hsp70 molecular chaperone, lysosomes and protesomes are connected each other in macroautophagy –mediated proteolysis in human RPE cells.
The role of electrophysiology
Authors: HOLDER GE
Published: October 2007

Purpose: To demonstrate the role of electrophysiological assessment in the investigation and management of the patient with photophobia, or whose vision is worse under bright lighting conditions.

Methods: The ISCEV standard techniques for ERG, PERGm, mfERG and EOG recording will be described.

Results: Selected cases will be used to illustrate the value of the objective data provided by electrophysiology.

Conclusions: The objective data provided by electrophysiological assessment is important to the assessment, diagnosis and management of this group of patients.
Application of structured illumination techniques to corneal microscopy
Authors: REQUEJO‐ISIDRO J , PEREZ‐ESCUDERO A , MARCOS J
Published: October 2007

Purpose: The microscopic study of corneal structures has always been a challenge for ophthalmologists and researchers. The inherent transparency of the cornea and the strong out‐of‐focus background are the main obstacles for achieving high‐contrast images. In the past few years traditional approaches based on the confocal principle have benefited enormously from the advances in scanning and detection technologies, but at the expense of an increasing complexity.

Methods: As an alternative approach to the confocal principle, the use of different patterns (structured) of illumination to retrieve the in‐focus features in an image may be advantageous for in‐vivo imaging. It has been shown that structured illumination (SI) microscopy allows optical sectioning with at least the same resolution as standard confocal microscopy. Image acquisition is potentially faster, as optical sections of the whole field of view are obtained after acquisition of two or three widefield images rather than scanning every point in the field of view. In spite of it, the overall performance of these techniques may be affected by noise features that are particular to SI imaging.

Results: We report on the application structured‐illumination microscopy to the field of ocular microscopy. To the best of our knowledge, this is the first time that corneal microscopy using structured illumination has been demonstrated. Enucleated porcine eyes have been used to study SI‐specific noise behaviour. Its implications for ophthalmic SI microscopy will be discussed.
Motion of the scattering sites in the ocular fundus during transpupillary thermotherapy
Authors: ROVATI L , CATTINI S , VIOLA F , STAURENGHI G
Published: October 2007

Purpose: Our aim was to detect motion of scattering sites during transpupillary thermotherapy (TTT) using diffusing‐wave‐spectroscopy technique

Methods: The experiment was performed on a rabbit fundus. Motion of scattering sites in the fundus was monitored during TTT. A contact lens was used for easy fundus observation and guidance of the treatment and probe laser radiation. The treated area diameter was ± 4 mm. The optics of the diffusing‐wave‐spectroscopy system were integrated into a standard ophthalmic microscope to allow a real time recording of the intensity of the light scattered by the heated scattering centres.

Immediately before, uring (at 5 sec intervals) and after TTT, autocorrelation functions were acquired To exclude possible visible alteration of the tissues at the end of the treatment, an ophthalmologist observed the eye fundus.

Results: The experiment showed that in the retina and RPE, temperature‐induced scatterers motion increases monotonically during TT according to an exponential trend with time constant of ± 20 seconds. The choroidal diffusion coefficient showed a clear sharp step‐down in response to temperature rise. This trend does not reflect the trend of temperature but different boundary conditions or optical properties of the scatterers.

Data showed also a slight increase in choroidal blood velocity upon heating of the fundus.

Conclusions: These experiments showed the ability of the system to detect motion of scattering sites in the ocular fundus layers. We observed the temperature induced dynamics of retina and choroid scattering centers. Speculatively, the choroidal diffusion coefficient trend could be related to a resctriction of the choroidal vasculature in response to increasing fundus temperature
An overview of the pathogenesis of glaucomatous optic neuropathy
Authors: GUNGOR K
Published: October 2007

Glaucoma, clinically, is characterized by degeneration of the optic nerve and progressive visual field loss, associated with elevated intraocular pressure (IOP). The exact cause of glaucomatous optic neuropathy is not well established, although many risk factors have been determined including elevated IOP, family history, race, age, systemic diseases and myopia. Elevated IOP is the most investigated factor among others because it is the main well‐known treatable one for glaucoma.

The primary components of glaucomatous optic neuropathy are spesific changes in the optic nerve head and in the retina. In the optic nerve head, these can be classified as axonal and non‐axonal effects (alterations in extracellular matrix and astrocyte ). In the retina, retinal ganglion cells appear to undergo morphologic changes before cell death.These changes give a result as an decrease in number of retinal ganglion cells and a decrease in visual acuity.

Nowadays, lowering IOP alone is not sufficient for the long‐term stabilization of visual functions in glaucoma patients. Some abnormalities in optic nerve head and retina may affect relative susceptibility to IOP and explain progressive optic nerve damage and visual field loss, although adequate IOP control. Moreover, optic disc excavation and nerve fiber layer losses of up to 40% have been shown to occur, prior to visual field loss has been determined.

In addition to vascular and mechanical theory for glaucomatous optic neuropathy include excitotoxic damage, insufficiency in neuron growth factors, immune‐mediated neuron destruction, and oxidative stress. The exact role of these factors and their effects on glaucomatous damage and apoptosis is still controversial.
Optic nerve injury models in the rat
Authors: TUGLU I
Published: October 2007

Glaucoma is a degenerative disorder of the optic nerve which can be secondary to many diseases and the pathology occurs at the optic nerve head (ONH). It is important to know the effects of cell types, cell interactions, the trophic factors, receptors, channels, and matrix molecules in glaucoma. Research on the optic nerve in rats, mice, and nonhuman primates are necessary not just neurons in retina and optic nerve but also in central nervous system.

Experimentally‐induced animal models help in understanding how retinal ganglion cells (RGC) die and how ON take place in this process. Special care must be taken to select controls and to use adequate number of animals. Experiments should be performed to understand the mechanism of pressure‐induced optic nerve damage and protect the optic nerve in glaucoma. An effective model should allow for the obstruction of aqueous humor outflow in order to raise IOP and for monitoring of intraocular pressure. Raised intraocular pressure, altered ocular perfusion, loss of auto regulation, alteration of vascular structure and characteristics of the blood‐brain barrier at the optic disc are also

possible candidates in the pathogenesis of glaucoma. Animal studies indicate a response in

oxidative metabolism to varied IOP and mean arterial blood pressure, and that low blood pressure leads to loss of autoregulation and ischemia of the optic nerve head.

A number of techniques for increasing the intraocular pressure in rat are available. One of them involves sclerosing the trabecular meshwork using hypertonic saline. By cannulating the

veins and injecting the corrosive saline retrogradely into the canal of Schlemm, it is possible to scar and close up the trabecular meshwork. Intraocular pressure elevates in approximately a week and lesions begin to develop. The lesions seen in the rat optic nerve following this procedure includes a decrease in axon density and an increase in vesicular bodies and vacuoles that is most prominent in the superior region of the optic nerve.

We also carried out different models of rat studies either by damaging the ON mechanically or by ischemia to show the histological alterations in the ONH and retina. We also investigated the effects of oxidative stress and apoptosis on these alterations. Understanding the mechanism of nerve damage in these different models may provide new insights into the pathogenesis of human glaucoma.
Electrophysiology as a diagnostic tool
Authors: HOLDER GE
Published: October 2007

Purpose: To describe the use of electrophysiological investigation in the assessment of patients with inherited retinal disease.

Methods: The techniques used to elicit ISCEV Standard ERGs, PERG, EOG and mfERG will be discussed. In addition, reference will also be made to additional techniques such as ON‐/OFF‐ response recording and S‐cone ERGs

Results: Selected cases will be used to illustrate the value of electrophysiological investigation in the assessment and characterisation of inherited retinal disease. Particular emphasis will be placed on those disorders where the diagnosis is made by electrophysiology.

Conclusions: The objective assessment of retinal, macular and RPE function using electrophysiological techniques is indispensable to the running of an inherited retinal disease clinic. Electrophysiology is likely to be the "gold‐standard" outcome measure in studies of potential therapeutic interventions
Preoperative assessement before surgery of the lacrimal pathway
Authors: ELOY P , LEVECQ L
Published: October 2007

Methods: Dacryocystorhinostomy (DCR) consists of diverting the lacrimal flow into the nasal cavity through an opening made surgically in a standard fashion at the level of the frontal process of the maxilla. Indication for surgery is low obstruction of the lacrimal pathway resistant to the medical treatment.

To make the differential diagnosis between hypersecretion and epiphora, a high or a low obstruction, an anatomical or a functional obstruction of the lacrimal pathway, a preoperative evaluation of all the lacrimal pathway is mandatory.

The authors present their experience and comment the technique, the advantages and limits of different investigations such as the ophthalmological examination including Jones tests 1 and 2, and seringing, dacryography, dacryoscan, scintigraphy of the lacrimal pathway and also give some words about the endoscopy of the lacrimal pathway. They also present the results of a survey conducted among the Belgian ophthalomologists confirming that only a minority of them perform a series of investigations (imaging) before a DCR.
Combined surgery: endoscopic transcanalicular DCR and balloondilatation technique
Authors: JAVDANI Z , ADAM J , MEYER R , EMMERICH KH
Published: October 2007

Purpose: Combined surgery technique for high rate percentage of success in trans‐canalicular dacryocystorhinostomy or a balloon dilatation technique alone.

Methods: In this approach, transcanalicular endoscope with micro drill performing surgery like usual, dilatation of the opened channel with balloon dilatation and following injection of Healon‐5 in the lacrimal duct are employed to reduced the risk of failure. This method is investigated through the two cases. Percentage of success of balloon catheter overall is estimated between 25% to 90% depends on the partial or complete obstruction. In the most of these cases of failure, cannulation was not possible because of complete obstruction. This problem might be solved by using micro drill before balloon dilatation technique.

Results: In 2 cases, no more epiphora after 6 months follow‐up were observed. (100 % of success rate was achived by 2 patients). However, more cases are needed to show the real succes rate.

Conclusions: Performing transcanalicular DCR using micro drill and following balloon dilatation of the naso‐lacrimal duct following an injectable product like Healon‐5 or healon‐gv (by which will hold the nasolacrimal duct open and will stay in the duct for a short period) can diminish the failure of balloon dilatation technique. In this way, the forming of synechia in all the duct from the punctum to the end of the distal duct will be reduced.
Glare as parameter of quality of sight
Authors: TASSIGNON MJ , ROZEMA JJ
Published: October 2007

The concept of glare, as determined by the Oculus C‐Quant device, is discussed in detail. Its clinical use and limitations are highlighted and correlations with other ocular parameters are investigated. As illustration the use of the C‐Quant in the University Hospital Antwerp for cataract and refractive cases is given, as well as for more challenging cases (postoperative complications, perforations ...).
Experimental models of ocular inflammation: an overview
Authors: BODAGHI B
Published: October 2007

Since the description of the role of different retinal antigens associated with intraocular inflammation in the early 70’s, a great number of experimental models have been developed in order to evaluate the pathophysiology of this auto‐inflammatory condition but also the efficacy of different therapeutic strategies. Experimental autoimmune uveitis is the most common murine model which has been used for these purposes. Disease development is mediated by Th1 CD4 cells specific for various retinal autoantigens. However, the role of these cells in the pathogenicity of uveitis remains poorly understood, because it is difficult to follow their activation and migration. Activated

macrophages, attracted by cytokine secretion, also cause retinal damage due to the release of cytotoxic oxygen and nitrogen metabolites, cytokines, and proteolytic enzymes.

Even though different issues have been raised and major advances have been achieved, we are still lacking well‐defined and appropriate relevance of these models for different human conditions. This is the main difficulty encountered by the research groups who try to use experimental models for the understanding and treatment of specific human entities. Only acute uveitis is obtained in the majority of classical models in rodents. Only a few models, in which a specific antigen may trigger the auto‐inflammatory reaction without other associated factors, are available.

It is highly important to revisit the experimental models of ocular inflammation in order to define the most appropriate ones for each human entity.
Prognostic tools for visual acuity in primary rhegmatogenous retinal detachment
Authors: ROLDAN‐PALLARES M , MUSA AS , BRAVO‐LLATAS C , HERNANDEZ‐MONTERO J , FERNANDEZ‐DURANGO R
Published: October 2007

Purpose: To study the influence of central retinal artery (CRA) blood velocities, intraocular pressure (IOP) and Endothelin‐1 (ET‐1) on visual acuity (VA) of primary rhegmatogenous retinal detachment (RD)

Methods: This is a prospective interventional clinical study of 66 patients undergoing scleral buckling (SB) procedure, with reattachment of the retina 8 months after surgery.

CRA Doppler sonography parameters and IOP were measured before SB. Immunoreactive (IR) ET‐1 was assayed (radioimmunoassay) in plasma and subretinal fluid (SRF). Snellen VA and fundus examination were checked before and 8 months after surgery. Stepwise multivariate linear regression analysis allowed us to find models for VA

Results: IOP and CRA end diastolic velocity (EDV) explains preoperative VA (R2=0.509, p<0.0001). Preoperative VA, existence of PVR, CRA EDV and plasma IR‐ET‐1 (in PVR) explains postoperative VA (R2=0.908, p<0.0001). But, preoperative VA, SRF IR‐ET‐1 and plasma IR‐ET‐1 improves last model in PVR

Conclusions: Preoperative VA, existence of PVR and CRA EDV explains 90% (88% in PVR) of the variability of postoperative VA, but a model with preoperative VA, SRF IR‐ET‐1 and plasma IR‐ET‐1 explains 90% of it in PVR

(Supported by grants: FIS PI 040446 and DGES 97/0028)