Karl Anders Knutsson

Ranibizumab in the treatment of patients with visual impairment due to diabetic macular edema

Diabetic macular edema is the major cause of visual acuity impairment in diabetic patients. The exact etiopathogenesis is unknown and, currently, grid/focal retinal laser photocoagulation represents the recommended treatment. It has been demonstrated that vascular endothelial growth factor (VEGF) plays a key role in the pathogenesis of diabetic macular edema by mediating vascular permeability and accumulation of intracellular and extracellular fluid, and thereby represents an appealing candidate as a therapeutic target for the treatment of diabetic macular edema. The advent of intravitreal anti-VEGF drugs has opened up a new era for the management of diabetic macular edema. At present, three anti-VEGF substances are available for routine clinical use, ie, pegaptanib, ranibizumab, and bevacizumab. The aim of this review is to summarize the evidence supporting the use of ranibizumab in clinical practice. Most of the studies analyzed in this review are prospective, controlled clinical trials that have focused on documenting the therapeutic effect of ranibizumab and its safety, providing encouraging results.

Accidental injection of dexamethasone intravitreal implant in the crystalline lens

new onset CMO (10%). The proportion of relapses treated with systemic steroids significantly reduced from 70% prediabetes to 56% postdiabetes diagnosis. Adding local steroid injection while on systemic steroids increased from 4% to 15% (p = 0.003, chi-square test). No significant difference was observed in the uveitis relapse treatment success preversus postdiabetes diagnosis (Table 1). Of the 96 eyes with uveitis and DM, one eye developed a clinically significant macular oedema after 3 years and required grid laser treatment, while seven eyes of six patients (7.3%) developed non-proliferative diabetic retinopathy, which occurred at a median of six (range, 2–11) years. While one previous study explored the visual outcome of 36 patients with diabetes who later developed uveitis (Oswal et al. 2013), our study further explores the synergistic effect of uveitis and diabetes by examining the effect of newly diagnosed diabetes on the eyes with uveitis and the effect of diabetes on uveitis treatment strategies. In conclusion, the concurrent diagnosis of DM in uveitis patients is associated with a significant reduction in visual acuity within the first 2 years. More uveitis relapses were treated with local steroid injection rather than increasing systemic corticosteroid dose, without affecting the ability to control uveitis relapses. It is important to optimize treatment protocols for DM and uveitis when occur concurrently.

Modified big-bubble technique compared to manual dissection deep anterior lamellar keratoplasty in the treatment of keratoconus

To evaluate the clinical findings and results of manual dissection deep anterior lamellar keratoplasty (DALK) compared to a modified big‐bubble DALK technique in eyes affected by keratoconus.

Deep anterior lamellar keratoplasty using an original manual technique

Aims To evaluate the clinical findings and visual outcomes of deep anterior lamellar keratoplasty (DALK) using an original manual dissection technique. Methods 288 eyes (268 patients) with corneal pathologies without endothelial involvement were treated by DALK using an original manual dissection technique guided by a calibrated knife incision based on ultrasonic pachimetry values. Clinical records were examined retrospectively at 2 months, 6 months, 1 year and 2 years. The following outcomes were measured: visual acuity, topographic parameters, endothelial cell density and recipient stromal residue thickness. Results At the 2-year postoperative follow-up, the mean logarithm of the minimum angle of resolution best spectacle corrected visual acuity (BSCVA) was 0.131±0.087 and topographic astigmatism was 2.87±1.57 diopters. In 12 cases (4.2%) a perforation of Descemets membrane required conversion of the procedure to penetrating keratoplasty. Mean optical coherence tomography (OCT) residue thickness (measured in 82 eyes with OCT Visante) was 31.63±24.57 μm; lower values of recipient residue thickness were significantly associated with higher BSCVA (Spearman coefficient 0.635, p< 0.001). Conclusion DALK using a dry manual dissection technique provides visual, refractive and clinical results comparable to other deep lamellar techniques. Eyes with lower values of recipient residue thickness are associated with better visual acuity.

Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa treated with intravitreal bevacizumab.

PURPOSE To describe a case of juxtafoveal choroidal neovascularization (CNV) occurring in a patient affected by retinitis pigmentosa (RP), treated with intravitreal bevacizumab over a 12-month follow-up. METHODS A 66 year-old woman referred to our center for visual acuity deterioration was diagnosed as having classic juxtafoveal CNV associated with RP. The patient was treated with intravitreal bevacizumab, and was regularly monitored every month. RESULTS At the end of the 12-month follow-up, best corrected visual acuity changed from 20/200 to 20/100 in the affected eye. Five intravitreal bevacizumab injections were required to obtain the stabilization of the CNV. CONCLUSIONS Intravitreal bevacizumab is effective in producing juxtafoveal CNV stabilization and visual acuity improvement in a patient affected by RP, over a 12-month follow-up. Future studies are required to ascertain the best therapeutic approach for CNV complicating RP.

Intravitreal bevacizumab for juxtafoveal choroidal neovascularization secondary to multifocal choroiditis

Purpose: To assess the effects of intravitreal bevacizumab injections in the treatment of juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Methods: Prospective interventional case series. Fourteen patients (14 eyes) affected by juxtafoveal choroidal neovascularization secondary to multifocal choroiditis were examined. All patients underwent a complete ophthalmologic examination, including measurement of best-corrected visual acuity using Early Treatment Diabetic Retinopathy Study charts, optical coherence tomography, and fluorescein angiography. The protocol treatment included a first injection, followed by repeated intravitreal bevacizumab injections over a 12-month follow-up period on the basis of optical coherence tomography parameters and angiographic features. Results: Mean best-corrected visual acuity changed from 0.41 logarithm of the minimum angle of resolution (approximately corresponding to 20/51 Snellen equivalent), at baseline, to 0.16 ± 0.13 logarithm of the minimum angle of resolution (approximately corresponding to 20/28 Snellen equivalent), at the 12-month examination (P < 0.002). A functional improvement of at least 3 Early Treatment Diabetic Retinopathy Study lines was achieved by 6 eyes (43%) at the 12-month examination. Mean central macular thickness at baseline was 318 &mgr;m, reducing to 239 &mgr;m at the 12-month examination (P < 0.001). No eye showed choroidal neovascularization extension to the fovea. Conclusion: Intravitreal bevacizumab is a beneficial treatment for juxtafoveal choroidal neovascularization associated with multifocal choroiditis. Further studies are warranted to confirm these preliminary results.

Primitive retinal vascular abnormalities: tumors and telangiectasias.

Primitive retinal vascular abnormalities are benign conditions of the retinal circulation that comprise vascular tumors and telangiectasias. The principal vascular tumors of the retina include retinal capillary hemangioma, cavernous hemangioma of the retina, racemose hemangiomatosis of the retina and retinal vasoproliferative tumor, while primary retinal telangiectasias include Coats’ disease, Leber’s miliary aneurysms and idiopathic juxtafoveal telangiectasias. In most cases, these alterations result in significant visual impairment due to exudation determined by the structural abnormalities of the retinal vasculature. The aim of this review is to assess the different clinical and diagnostic features of the single pathological entities and to discuss the available treatment modalities including the onset of intravitreal antivascular endothelial growth factor therapy.

Intravitreal bevacizumab for choroidal neovascularisation in serpiginous choroiditis

Purpose To assess the effects of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularisation (CNV) secondary to serpiginous choroiditis (SC). Design Non-randomised, interventional case series. Participants Seven patients (seven eyes) affected by juxtafoveal CNV (six eyes) and subfoveal CNV (one eye) associated with SC were recruited. Methods Each patient underwent an ophthalmological examination, including measurement of best-corrected visual acuity (BCVA), fluorescein angiography (FA) and optical coherence tomography (OCT). After a first IVB injection (1.25 mg), patients were evaluated monthly over a 12-month follow-up. Further re-treatments were performed on the basis of detection of any type of fluid on OCT and/or presence of leakage on FA. The primary outcome considered was the median change in BCVA, as well as the proportion of eyes gaining at least 5 and 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at the end of the 12-month follow-up. Secondary outcomes included median changes in central macular thickness (CMT) and number of injections over the planned follow-up. Results Median BCVA changed from 0.3 to 0.4 LogMAR. A functional improvement of at least 5 and 10 ETDRS letters was obtained in two eyes (28%) and one eye (14%), respectively, at the 12-month examination. Four eyes (57%) had stable BCVA, whereas one eye (14%) experienced a two-line decrease. Median CMT at baseline was 261 μm, decreasing to 196 μm at the 12-month examination. The median number of IVB injections was 1 in 12 months. Conclusions IVB can achieve anatomical stabilisation of CNV secondary to SC, avoiding a decline in visual acuity, in almost 90% of cases over a 12-month follow-up.

Macular hole after injection of dexamethasone intravitreal implant for macular oedema due to central retinal vein occlusion

acizumab has been shown to be effective in treating ROP in the BEATROP trial (Mintz-Hittner et al. 2011). However, bevacizumab escapes from the vitreous into the general circulation and reduces systemic VEGF concentrations for weeks to months (Lee et al. 2011; Sato et al. 2012). Thus, there are concerns about systemic complications, particularly in infants with a very low body weight and rapidly developing tissues. Ranibizumab is an alternative anti-VEGF antibody with similar efficacy as bevacizumab but with the advantage that it does not alter systemic VEGF levels in adults (Carneiro et al. 2012). In ROP treatment, ranibizumab has rarely been used. We present a case report of a very premature infant with ROP that received ranibizumab injections in both eyes. We assessed the effect of ranibizumab on the VEGF concentration in the serum. A male infant born at a gestational age of 22+5 weeks and a body weight at birth of 305 g presented with ROP stage 3 in all quadrants in zones 1–2 with plus disease in both eyes. No tractional retinal detachment or vitreous haemorrhage was present. At the time of diagnosis, the infant was in the 33rd gestational week. Because the avascular zone was located at the border of zones 1 and 2, an intravitreal anti-VEGF therapy with 0.2 mg ranibizumab was chosen for both eyes under local anaesthesia. The parents gave written informed consent on the off-label use of the drug. Plasma samples for routine laboratory tests were collected preoperatively, as well as 1 week, 3 weeks and 4 weeks postoperatively. For safety monitoring, serum VEGF levels were determined by multiplex bead analysis (Luminex, Austin, TX, USA). The procedure did not require approval by the local ethics committee. Three days postoperatively, the plus disease had resolved in both eyes. After one week, regular vascularization of the former avascular area had begun and proceeded in the later course. No tractional retinal detachment and no retinal haemorrhage occurred. Systemic VEGF level was 170.9 pg ⁄ml preoperatively. Postinjection of ranibizumab, systemic VEGF levels were 67.3 pg ⁄ml, 0 pg ⁄ml and 205.8 pg ⁄ml at 1 week, 3 weeks and 4 weeks, respectively (Fig. 1). The detection limit of our assay was <2 pg ⁄ml. In this infant, ranibizumab suppressed systemic VEGF levels below detection limit for about 2 weeks reaching a nadir at 2–3 weeks after intravitreal injection. This suppression may be due to an impaired blood–retinal barrier at this age as ranibizumab does not change systemic VEGF levels in adults (Carneiro et al. 2012). A case series of 11 eyes treated with intravitreal bevacizumab for ROP reported a suppression of systemic VEGF levels for at least 7 weeks postinjection (Lee et al. 2011). In contrast, we show that 4 weeks after bilateral injection of ranibizumab, systemic VEGF has returned to normal levels again. Our data suggest that intravitreal ranibizumab also suppresses systemic VEGF, and therefore systemic side effects cannot be excluded. If antiVEGF treatment is considered, ranibizumab may be the better choice, as systemic VEGF suppression seems to be shorter than with bevacizumab.

Corneal collagen cross-linking in paediatric patients affected by keratoconus

Background/aims To evaluate the effectiveness of corneal collagen cross-linking (CXL) in paediatric patients. Methods Fifty-two eyes of 43 paediatric patients with progressive keratoconus were enrolled in a prospective cohort study. Corneal CXL was performed using a conventional technique with instillation of 0.1% riboflavin solution containing dextran 20% for 30 min during the soaking phase and during the 30 min ultraviolet A irradiation (3 mW/cm2). Visual outcomes, topographic keratometry, maximum keratometry (K-max), refractive astigmatism, demarcation line and endothelial cell density were measured postoperatively. Results A significant decrease of K-max from 59.30±7.08 to 57.07±6.46 (p<0.001) was observed 2 years after treatment. Uncorrected visual acuity improved from 0.59±0.41 LogMAR (logarithm of the minimum angle resolution) to 0.46±0.33 LogMAR (p=0.06) 2 years after the procedure, while best spectacle corrected visual acuity improved from 0.17±0.11 LogMAR to 0.15±0.12 LogMAR (p=0.17). Twenty-five eyes had K-max values of 60 dioptres (D) or greater. In this subgroup, K-max significantly decreased from 64.94±4.99 D to 62.25±4.42 D at 2 years (p<0.001). The demarcation line of the CXL treatment had a mean value of 249±74 µm and did not show a significant correlation with K-max flattening (Spearman r=0.019, p=0.899). Endothelial cell density remained stable 2 years after the procedure, changing from 2800±363 to 2736±659 cells/mm2 (p=0.90). Conclusion CXL is an effective treatment for avoiding keratoconus progression in paediatric patients. The procedure is safe and successful in stabilising keratoconus in eyes with more advanced forms of the disease, characterised by topographic K-max values greater than 60 D.