Intravitreal Injection of Beva Cizumab and Focal Laser Photocoagulation for Choroidal Metastatic Tumors- A Case Report

To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO). Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit-lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2-4, 8 and 12 weeks post-injection. Best corrected VA and CRT were analysed in both groups. In the non-pretreated group, mean BCVA improved from 0.76 +/- 0.33 (baseline) to 0.57 +/- 0.30 and 0.54 +/- 0.27 at 2-4 weeks and 8 weeks post-injection, respectively (p = 0.02, p = 0.014, paired t-test). Mean CRT decreased from 632.4 +/- 196.0 microm (baseline) to 392.3 +/- 113.6 microm and 370.4 +/- 141.7 microm at the same time-points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 +/- 0.30 (baseline) to 0.53 +/- 0.33 at 2-4 weeks post-injection (p = 0.01), and mean CRT decreased from 583.9 +/- 180.7 microm (baseline) to 404.1 +/- 197.9 microm at 2-4 weeks post-injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post-injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side-effects developed during follow-up. One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

Objective To compare the efficacy of intravitreal injection of ranibizumab and bevacizumab in the treatment of pathological myopia choroidal neovascularization (PM-CNV). Methods It is a retrospective case study. Seventy-nine patients (79 eyes) with PM-CNV were enrolled in this study. There were 26 males (26 eyes) and 53 females (53 eyes), with the mean age of (30.77±5.53) years. The best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscope, fundus color photography, fundus fluorescein angiography, and optical coherence tomography (OCT) were performed. BCVA was recorded as logarithm of the minimum angle of resolution (logMAR). The central retinal thickness (CMT) was measured by OCT (Cirrus HD-OCT). The eyes were divided into bevacizumab treatment group (38 eyes) and ranibizumab treatment group (41 eyes). There was no difference of the mean logMAR BCVA, intraocular pressure and CMT between two groups (t=−0.467, −1.983, 1.293;P=0.642, 0.051, 0.200). The eyes in bevacizumab treatment group were treated with bevacizumab 0.05 ml (1.25 mg), and the eyes in ranibizumab treatment group were treated with ranibizumab 0.05 ml (0.5 mg). Times of injection between two groups were compared. The changes of intraocular pressure were observed at 1, 7 days and 1 month after treatment. The changes of logMAR BCVA and CMT at 1, 3, 6, 12 and 24 months after treatment and systemic adverse reactions occur were compared. Results At the 1, 3, 6, 12 and 24 months after treatment, the mean logMAR BCVA of the bevacizumab treatment group and the ranibizumab treatment group was significantly improved than that before treatment (F=132.374,P<0.01). There was no significant difference in the mean logMAR BCVA at different time points between the two groups (F=0.095,P=0.759). The mean CMT of the two groups was lower than that before treatment (F=151.653,P<0.01). There was no significant difference in the mean CMT between the two groups (F=0.332,P=0.566). No retinal detachment, endophthalmitis, cataract and persistent high intraocular pressure were associated with drug, injection-related eye and systemic adverse events during follow-up. Seven eyes had conjunctiva bleeding after treatment, 11 patients (11 eyes) complained of shadow floaters after treatment. Conclusion Intravitreal injection of bevacizumab or ranibizumab can equally effectively improve the visual acuity and reduce the CMT of PM-CNV patients. Key words: Choroidal neovascularization/therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Myopia, degenerative/complications

Photodynamic therapy for choroidal metastasis from lung adenocarcinoma

To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal injection of bevacizumab 1 mg, which was followed by two more injections at 6-week intervals. Fundus photography and optical coherence tomography (OCT) were carried out at baseline immediately before injection and at 1, 2.5 and 4 months after the first injection. Outcome measures were best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, macular volume, foveal subfield thickness and vessel diameter measurement. Intravitreal administration of bevacizumab was followed by a mean increase in BCVA of 7.3 +/- 17 (mean +/- standard deviation) letters between baseline and month 4, which was 1 month after the last injection (p < 0.0001). This was accompanied by a reduction in mean macular volume from 9.90 +/- 1.9 mm(3) to 8.96 +/- 2.4 mm(3) (p = 0.002) and in foveal subfield thickness from 447 +/- 117 microm to 388 +/- 117 microm (p = 0.03). Two eyes with early proliferative diabetic retinopathy lost all signs of proliferation without any evidence of fibrosis. Although there was a trend towards vasoconstriction, the changes in vessel diameters (arteries and veins) after 4 months of intravitreal Avastin injection were not statistically significant (p = 0.9 and p = 0.17, respectively). Foveal thickness in non-injected fellow eyes with DMO changed from 428 +/- 153 microm at baseline to 383 +/- 151 microm at 4 months (p = 0.1), which did not reach statistical significance. Intravitreal bevacizumab 1 mg every 6 weeks was followed by a moderate reduction in DMO without normalization of foveal and macular thickness. Our observations suggest that a larger study where patients are examined sooner after injection is needed to elucidate the potential relationship between changes in retinal vessel diameters and thickness changes in DMO.

June at a Glance

Choroid metastasis from primary lung cancer is rare and has a poor prognosis. It can be treated with an external beam of radiation or by laser photocoagulation. However, visual defects or blindness are possible complications related to radiotherapy. Chemotherapy for such a condition has not been widely reported. We report a 26-year-old patient who had stage IV lung adenocarcinoma and suffered from progressive blurred vision during a scheduled chemotherapy regimen. Fundoscopy, fluorescence angiography and optic coherence tomography indicated choroidal metastasis of both eyes. We prescribed a platinum double chemotherapy regimen with pemetrexed and cisplatin. A follow-up examination demonstrated complete remission of the choroid metastasis. Herein, we report the first case of lung cancer with choroid metastasis that underwent complete remission after pemetrexed administration. We share our experience and conduct a literature review. (Thorac Med 2012; 27: 159-166)

To study the relationship between intraretinal optical coherence tomography (OCT) and fluorescein angiography (FA) findings in eyes with diabetic macular oedema (DMO). We carried out a retrospective observational case series. Thirty eyes with previously untreated DMO underwent FA and OCT. The same ETDRS template was overlaid on the FA images in order to compare OCT and FA. Transfoveal linear high-resolution OCT scans (at the 0- and 90-degree meridians) and FA pictures were compared according to the ETDRS rings. Six distinct patterns of intraretinal changes in OCT correlated with changes in FA: (a) focal angiographic leakage did not correspond to any obvious intraretinal abnormality in OCT in four eyes; (b) localized thickening of the outer nuclear layer in OCT corresponded to focal leaking microaneurysm (focal oedema) in FA in 11 eyes; (c) diffuse thickening of the outer nuclear layer in OCT corresponded to diffuse angiographic leakage in 21 eyes; (d) cystoid expansion of the outer nuclear layer was found in seven eyes with a petaloid angiographic pattern of leakage; (e) cystoid expansion of the inner nuclear layer was found in relation to honeycomb angiographic oedema in five eyes, and (f) serous detachment of the fovea in OCT did not correspond to any distinct finding in FA in four eyes. Intraretinal abnormalities found in OCT correlate systemically with changes in FA. Very early DMO morphological changes may be seen better with FA than with OCT. Serous detachment of the fovea is seen in OCT, but not in FA. The combination of OCT and FA is useful in facilitating understanding of the pathophysiological changes that occur in DMO.

To compare efficacy of intravitreal bevacizumab versus triamcinolone in the treatment of diffuse diabetic macular oedema (DME). This retrospective nonrandomized study includes 60 patients with diffuse DME treated with at least one intravitreal triamcinolone injection (ITA) or intravitreal bevacizumab injection (IBe). Regression analysis was performed for pretreatment, glycosylated haemoglobin level, visual acuity (VA) at baseline and central macular thickness (CMT) at baseline. After 1-, 3-, 6- and 9-month follow-up, there was no significant change in either VA or CMT treatment in the ITA and IBe groups. There was no statistically significant difference between the two treatment groups. Changes in CMT and VA in the subgroups were not significant. Only predictive factor independent of HbA1c level and VA was CMT at baseline in both treatment groups. The thicker CMT at baseline, the higher was reduction in CMT. After 1 month, the IBe group had a significantly higher decrement than the ITA group. In our study collective, neither IBe nor ITA treatment was able to improve VA during follow-up, significantly. CMT was reduced in both treatment groups, however not significantly. Our data demonstrates that reduction in CMT with either IBe or ITA treatment was significantly influenced by degree of CMT at baseline.

Objective To evaluate visual field changes every time after systemic bevacizumab (Avastin) therapy in patients with choroidal neovascularization (CNV) related age-related macular degeneration (ARMD). Methods Single-center, uncontrolled clinical study. Thirteen CNV related ARMD patients (15 eyes) with best-corrected visual acuity (BCVA) more than 0.1 were determined by indirect ophthalmoscope, fundus fluorescein angiography (FFA) and optic coherence tomography (OCT). All these eyes were underwent 6 times intravitreal injections of bevacizumab (1.25mg, 0.05ml) at 6 w to 12 w intervals. The follow-up investigation time was from 3 to 12 months. Record and analyze the mean visual sensitivity (MS), mean defect (MD) and loss variance (LV) changes before and 6w, 12w. 24w, 48w after injections. Results Take 0 week as a baseline, we found MS values of 24th week and 48th week revealing a remarkable increase (t values were 2.91, 3.69 respectively, P<0.05). MD values at 48th week decreased when compared with that at 0 week (t value was 1.35, P <0. 05). There were no statistically significant differences when compared LV values within these groups. Conclusions Repeatedly intravitreal injections of bevacizumab are benefit for visual acuity of neovascular ARMD, especially changes in MS and MD values of macular retina. Visual acuity would improve in most of the neovascularization ARMD after 4-6 times injections. Key words: Bevacizumab; Age-related macular degeneration (ARMD); Visual field

Objective To evaluate the efficacy and safety of intravitreal injection of Bevacizumab (Avastin) combined with laser photocoagulation in the patients of macular edema secondary to retinal vein occlusion (RVO).Methods This was a retrospective cases-series study.Thirty eyes of 30 RVO patients (branch RVO 20 eyes and central RVO 10 eyes) were erolled,aged from 34 to 79,with average of (57.3±8.9)years.The eyes were treated with intravitreal injections of Bevacizumab (1.25 mg) combined with laser photocoagulation.The treatment method of intravitreal injection had been conducted according to PrONTO study.Best corrected visual acuity (BCVA,ETDRS letters),fundus photography,optical coherence tomography (OCT) were committed at baseline and 1,3,6,12 months after intravitreal injection.The ETDRS letters and the central retinal thickness (CRT) by OCT were recorded.Changes in BCVA and CRT measurements from baseline at the various follow-up endpoints were assessed with paired t test.Spearman correlation coefficient was used to measure the strength of correlation between BCVA and anatomic changes.Results The mean number of the injections in the 30 patients was 3.9±1.9.The BCVA improved 3 or more lines in 16 eyes (54％),improved 1 to 2 lines in 10 eyes (33％),stabilized (±1 line or no change) in 4 eyes (13％) and none decreased.The average BCVA at baseline was (42±19) letters,and improved to (60±19) letters at 12 months (t=7.87,P＜0.05).The average of retinal thickness of macular foveal decreased from (616.7±177.0)μm at baseline to (268.9±l15.9)μm at 12 months (t=13.23,P＜0.05).BCVA 12 months post-treatment was correlated to BCVA pre-treatment (r=0.791,P＜0.01).Macular edema had no correlation with baseline and finally BCVA.21 eyes (70％) showed no observed macular edema by the last follow-up and the side effects were not observed during the follow-up.Conclusion The persistent and rebound macular edema found in Bevacizumab treatment had some common characteristics in FFA. Combined intravitreal injections of Bevacizumab and laser photocoagulation therapy seemed to be effective for managing some refractory macular edema secondary to RVO.The Bevacizumab and photocoagulation related adverse events are rare. Key words: Retinal vein occlusion; Macular edema; Vascular endothelial growth factor A; Bavacizumb; Laser therapy

The present study reports a case of a patient with choroidal neovascularization (CNV) associated with pseudoxanthoma elasticum (PXE). We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor (VEGF) inhibitor bevacizumab. The study also systematically searched the database for similar cases to provide a literature review. Data concerning the clinical features, treatment strategies and outcomes were extracted and analyzed. Retrospective interventional case report and systematic literature review. A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported. Examinations included best corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography and digital fundus photography. The patient managed with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (bevacizumab 1.25 mg/0.05 mL). The Cochrane Library, PubMed, OVID, and UpToDate databases were searched using the term pseudoxanthoma elasticum or Gronblad-Strandberg syndrome with the limits English. Articles that predated the databases were gathered from current references. Fundus examination revealed angioid streaks bilaterally and CNV in left eye (LE). After the patient underwent three intravitreal injections of bevacizumab, the LE showed absorption of the subretinal fluid and shrinkage of the CNV. Visual acuity (VA) was improved in her treated LE. Bevacizumab treatment was well tolerated with no adverse events reported. Approximately ten articles about 45 patients (49 eyes) describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search. In the present case, bevacizumab of an initial three injection loading dose, achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE. Literature articles concluded that the intravitreal application of anti-VEGF is highly efficient for improving and stabilizing the lesion as well as the eyesight. So we believe that anti-VEGF therapy can be a great choice of treatment for CNV secondary to angioid streaks related PXE.

Editor, Angioid streaks are irregular, radiating, jagged, tapering lines that extend from the peripapillary area into the peripheral fundus that may occur in isolation or as the ocular manifestation of a systemic disease. Linear breaks or dehiscence in a thickened, calcified and abnormally brittle Bruch's membrane can be associated with choroidal neovascularization (CNV) and poor vision. Several treatments have been attempted with limited success and high rates of recurrence (Costa et al. 2003; Shaikh et al. 2003; Aras et al. 2004). We report a case of subfoveal CNV due to angioid streaks treated with intravitreal bevacizumab 1.25 mg. A 23-year-old man with angioid streaks was referred for subfoveal CNV in his right eye (OD). He had suffered visual loss in the left eye (OS) after minor trauma. Best corrected visual acuity (BCVA) was counting fingers at 2 m OD and 20/400 OS. Fundus examination revealed peripapillary angioid streaks in both eyes, a grey subfoveal lesion with subretinal haemorrhage and subsensory fluid OD and a large pigmented macular scar OS. Fluorescein angiography (FA) revealed a subfoveal classic CNV associated with leakage and peripapillary hyperfluorescence corresponding to the angioid streaks OD and a staining of disciform scarring with no active leakage in the macula OS. Optical coherence tomography (OCT) showed neurosensory serous detachment and type 2 CNV OD (1, 3). The patient was counselled as to the prognosis of his condition and treatment options. Photodynamic therapy was offered but not accepted and an intravitreal injection of bevacizumab 1.25 mg was administered. (A) Early and (B) late-phase fluorescein angiography images at baseline. Optical coherence tomography scans at 6-mm at (A) baseline and (B) 18 weeks post-injection. After 7 weeks, VA was 20/40 and some residual leakage was seen at the lesion margin on FA. The subject underwent a second injection. After 12 weeks VA was 20/30, fundus examination showed no subsensory fluid, and OCT and FA revealed no leakage (2, 3). (A) Early and (B) late-phase fluorescein angiography images at 18 weeks after treatment Choroidal neovascularization occurs in 70–86% of patients with angioid streaks and more than half have vision of 20/200 or worse after the age of 50 years. It has been suggested that laser photocoagulation might resolve CNV and help to stabilize VA or slow down visual loss, given the very high frequency of recurrence (Lim et al. 1993). Other therapies such as photodynamic therapy, Indocyanine green-mediated photothrombosis (IMP) and transpupillary thermotherapy have recently been proposed as alternative treatments for CNV associated with age-related macular degeneration (AMD) and others types of CNV but they do not appear to change the course of the disease and the visual prognosis is poor (Lim et al. 1993; Costa et al. 2003; Shaikh et al. 2003; Aras et al. 2004). This is the first case report of intravitreal injection of bevacizumab in a patient with subfoveal CNV with angioid streaks. Our patient demonstrated a significant improvement at 18 weeks, with VA of 20/30. There was no evidence of inflammation by either OCT or FA at this time-point. Vascular endothelial growth factor (VEGF) has been implicated as the major angiogenic stimulus responsible for neovascularization in AMD. Bevacizumab has shown promising results in off-label intravenous injections administered as salvage treatment (Rosenfeld et al. 2005). A formal prospective study is necessary to determine the safety and efficacy of intravitreal bevacizumab in the treatment of CNV.

Role of adjunctive laser photocoagulation in a clinical setting of invisible subretinal worm

Objective To study the effect of Transpupillary thermotherapy (TTT) on choroidal metastases. Methods Nine cases were enrolled in the study, male 2 and female 7 cases. Bilateral eyes were affected in 3 cases. The age of cases was 37-60yrs with averaged at 44.6 yrs. The visual acuity was ≤0.05 in 1 eye,0.06-0.2 in 2 eyes, 0.3-1.0 in 9 eyes. The metastatic tumor showed as a yellow-white flat lesions with retinal detachment in different extent on their surfaces. The number of the lesions was single in 2 eyes, 2 in 3 eyes, ≥3 in 7 eyes. The location of the lesions was at the posterior pole in 4 eyes, at the macular and its surrounding in 6eyes, around the disc in 2 eyes. The primary tumor was located at the lung and bronchus in 5 cases, at the breast in 3 cases, at the large intestine in 1 case. Indirect ophthalmoscope, fundus fluorescein angiography (FFA), ultrasound (A, B) and optical coherence tomography (OCT) were used for exam. Treatment was delivered via slit lamp using an 810 nm diode laser (Iridex) with 250 to 1000 mw, with average 510 mw; the spot size was 2.0-3.0mm, duration ranged from 60 s to 120 s. The lesions just turned into pale-white appearance after treatment. The number of laser spot was 2-6 with average 3.7 spots. The session for management was 1-6 with average 2.9. The interval between 2 sessions was 1-3 months. The lesion just underlying the fovea was combined with photodynamic therapy (visudyne) in 1 case. Results The lesions turned into a flat scar with pigmentation and fluid absorption after treatment. The visual acuity was improved in 2 cases, unchanged in 4 cases, declined in 6 cases. The visual decline was caused by the lesion underneath the fovea and secondary macular lesions. The fellow-up was 1-32 months with average 9.6 months. Conclusions TTT is rational for choroidal metastatic lesions and has definite effect with low cost. It is worth doing in the future. Early discovering and managing the lesions helped to protect the visual acuity of the patients. Key words: Transpupillary thermotherapy; Choroidal metastasis; Photodynamic therapy

Objective To observe the efficacy and safety of combined photodynamic therapy (PDT)with intravitreal ranibizumab injection in patients with polypoidal choroidal vasculopathy (PCV).Methots Twenty-four PCV patients (24 eyes) were enrolled in this retrospective case study.All patients were assessed by the examinations of Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart,color fundus photography,fundus fluorescein angiography (FFA),indocyanine green angiography (ICGA) and optic coherence tomography (OCT).The mean visual acuity was (33.41± 19.43) letters; the mean macular retinal thickness was (343.63 ± 88.60) μm.Patients received PDT first,and intravitreal injected ranibizumab 0.5 mg (0.05 ml) 72 hours later.Treatments were repeated as a single intravitreal injection of ranibizumab combined with or without PDT if the monthly follow-up indicated that it was necessary.The average follow-up period was 13.1 months.The average treatment times were analyzed for each eye.Systemic and ocular adverse events were observed.Visual acuity,macular retinal thickness and leakage of PCV before and after the treatment were analyzed.Results Intravitreal ranibizumab injections was repeated (2.8± 1.6) times per eye on average,and intravitreal injection of ranibizumab combined with PDT was repeated (0.4±0.5) times per eye on average.No systemic and ocular adverse effects were found during and after combined therapy.In the last follow-up,the mean visual acuity of ETDRS was (44.21±17.24)letters,improved by 10.8 letters (t=-4.77,P＜0.01).Visual acuity was improved in 11 eyes (45.8％) and stable in 13 eyes (54.2％).FFA and ICGA showed complete closed PCV in 17 eyes (70.8％),partial closed PCV in 7 eyes (29.2％).OCT image showed that the retinal edema was disappeared in 19 eyes (79.2％) and alleviated in 5 eyes (20.8％).The mean macular retinal thickness was (171.33±38.06) μm,which was 172.30 μm less than that of pre-treatment values (t =11.96,P＜ 0.05).Conclusion Photodynamic therapy combined with intravitreal ranibizumab injections for PCV is safe and effective,with visual acuity improvement,reduction of retinal edema and PCV leakage. Key words: Choroid diseases/therapy; Photochemotherapy; Antibodies, monoclonal